88
1 PROJECT FINAL REPORT Grant Agreement number: 604448 Project acronym: NANOMAG Project title: Nanometrology Standardization Methods for Magnetic Nanoparticles Funding Scheme: FP7 Period covered: from 2013-11-01 to 2017-10-31 Name of the scientific representative of the project's co-ordinator, Title and Organisation: Christer Johansson, Professor, RISE Acreo AB Tel: +46 (0)727 23 33 21 E-mail: [email protected] Project website address: www.nanomag-project.eu

PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

  • Upload
    others

  • View
    3

  • Download
    0

Embed Size (px)

Citation preview

Page 1: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

1

PROJECT FINAL REPORT

Grant Agreement number: 604448

Project acronym: NANOMAG

Project title: Nanometrology Standardization Methods for Magnetic Nanoparticles

Funding Scheme: FP7

Period covered: from 2013-11-01 to 2017-10-31

Name of the scientific representative of the project's co-ordinator, Title and Organisation:

Christer Johansson, Professor, RISE Acreo AB

Tel: +46 (0)727 23 33 21

E-mail: [email protected]

Project website address: www.nanomag-project.eu

Page 2: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

2

4.1 Final publishable summary report

4.1.1 Executive summary The NanoMag project objectives were to standardize and harmonize ways to measure and analyse the

data for magnetic nanoparticle (MNP) systems. NanoMag brought together Europe’s leading experts in;

synthesis of magnetic single- and multi-core nanoparticles, characterizations of magnetic nanoparticles

and national metrology institutes. In the consortium, we have gathered partners within companies,

metrology institutes, universities and research institutes, all carrying out front end research and developing

applications in the field of MNP systems. The NanoMag project was a for year project started in 2013 and

ended in 2017. The objectives of the NanoMag project has been to improve and redefine existing

analysing methods and in some cases, to develop new analyzing methods for MNPs. By using improved

manufacturing technologies, we have synthesized MNPs with specific properties that have been analysed

with a multitude of characterization techniques (focusing on both structural as well as magnetic properties)

and the experimental results was correlated between different analysis techniques, and we obtained a self-

consistent picture that describes how structural and magnetic properties are interrelated. In the NanoMag

project we have used almost all existing analysis techniques to study MNPs. The project has defined

standard measurements and techniques which are necessary for defining a magnetic nanostructure and

quality control. The areas we have studied in the NanoMag project was focused on biomedical

applications, for instance bio-sensing (detection of different biomarkers), contrast substance in

tomography methods (Magnetic Resonance Imaging and Magnetic Particle Imaging) and magnetic

hyperthermia (for cancer therapy). In the NanoMag project we have had an associated stakeholder

committee group (17 members) of companies and universities in the fields of synthesis of MNPs and

analysis techniques. These group have helped the NanoMag consortium in the different surveys we have

sent out to understand the industrial needs and challenges in the fields of MNP synthesis, standardization

and analysis methods. Four surveys were distributed to over 250 organizations and the answers were

analysed to improve our standardization work and strategies. During the project NanoMag members have

made substantial standardization contributions to ongoing ISO standardization work in the field of MNP

systems. For most of the measurement methods standardization procedures (SOPs), uncertainty budgets

and metrological descriptions has been developed. Over 50 new MNP systems (single- and multi-core

particles) have been synthesized in the project and also SOPs for the synthesis of MNP systems have been

developed. We have obtained improvements in reproducibility of MNP synthesis. In the project we have

developed new MNP products and MNP analysis methods as a result of the work in the project. To reach

out to the public with respect to basic MNP knowledge and MNP applications, four electronic-learning

modules has been developed and will be available also after the NanoMag project. Over 80 new

publications in international high impact journals and over 160 presentations and seminars have been

carried out by NanoMag partners. During the project we have also developed a clearer nomenclature in

order to describe structure and magnetic properties of MNPs and MNP ensembles. Surveys of

measurement methods for MNPs and their pros and cons, classification of these methods including also

classification of different types of MNP systems has been reported and published. In the project we have

used Monte-Carlo simulations in order to explain the experimental results, which have led to improved

modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be

used in the magnetic hyperthermia field). Round Robin measurements (same analysis methods on the

same MNP samples but in different labs utilizing the developed SOPs) using different types of MNP

systems have been carried and the result was promising.

Page 3: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

3

4.1.2 Project Context and Objectives

Activities and context of the NanoMag project can be seen below and which WP’s the activities belongs

to. The WPs are defined in figure 1 below.

• Synthesis of MNP with defined properties WP1/WP3

• Improvement of existing analysis methods WP2/WP4

• Development of new analysis methods WP2/WP4/WP6

• Understanding of structural and magnetic properties WP3/WP4/WP6

• Definition of standard measurements WP4/WP5

• Definition of magnetic nanostructures and quality control WP3/WP4/WP5

• Dissemination and exploitation WP7

• Administration and management WP8

The work-packages were organized and connected as shown in figure 1.

Figure 1 the work packages and how they are linked together.

The strategic objectives of the NanoMag project were:

• To identify analysis and characterization techniques that can be used as standardization

measurements in the field of magnetic nanoparticle research and development and that will provide

valuables tools to the manufacturing process of magnetic nanoparticles and the regulatory work on

magnetic nanoparticles.

• Use new or improved analysis techniques to control the properties of magnetic nanoparticles that

improve their specific application.

• Promote the standardization techniques so they can be used both in research as well in industry,

SME or large companies.

• Provide/enable a traceable route for novel characterization techniques from a laboratory research

towards the basis of new metrological standards, which do currently not exist in the area of

magnetic nanoparticles.

Page 4: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

4

The achievement of the strategic goals of the NanoMag concept requires the advancement in several

complimentary characterization technologies.

The specific technical objectives of the project were:

• Correlate the magnetic and structural properties of magnetic nanoparticles.

• Develop new analysis techniques and models in the field of magnetic nanoparticles.

• Improve the traceability of the total magnetic nanoparticle “life time” from manufacturing to the

specific application.

• To present standardized procedures for manufacturing magnetic nanoparticles with specific

properties, for instance the size and size distribution and the aggregation state for a given material.

The overall workflow in the project can be seen in figure 2 below.

Figure 2 The workflow in the NanoMag project

In the application work package (WP6) we tested the new synthesized optimized MNP systems for each

application area.

4.1.3 Main Scientific and Technical Results

The NanoMag project summarizing the actual results are listed below. Also, some recommendations for

future work are listed in bold.

MNP synthesis

• Comprehensive description of synthesis routes

• Extensive synthesis of MNP covering different synthesis routes and MNP properties

• MNP series with gradually changing parameters

• Reproducibility of MNP synthesis in different labs

Page 5: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

5

Improvement of existing analysis methods

• Overview and classification of MNP analysis methods

• SOPs and technical documentation

• Uncertainty budgets (in some cases)

Development of new analysis methods

• Numerical inversion techniques for reconstruction of distributed parameters

• Optical measurement of dynamic susceptibility

Understanding of structural and magnetic properties

• Comprehensive analysis of MNP series with gradually changing parameters

• Characterization of multi-core MNPs

• Neutron scattering measurements in combination with other characterization methods

Definition of standard measurements

• Metrological checklists

• SOPs and technical documentation

• Active participation in ISO/TC229 (ISO 19807 and PG14)

Definition of magnetic nanostructures and quality control

• Definition of structural concepts and terminology for single-core and multi-core particles

• Examples of comprehensive characterization of (complicated) MNPs, (e.g. nanoflowers)

• Quality control (Task 4.2 in the analysis work package WP4)

Dissemination and exploitation

• Stakeholder interaction (four online surveys, workshops)

• E-learning modules, four e-learning modules was developed in the project and available link from

NanoMag website and hosted at the NPL website

• Scientific publications

• Commercial exploitation of project results

• Follow-up project EMPIR MagNaStand (start 2017, coordinated by PTB)

• PR activity (EuroNanoForum 2015, NanoMag was voted to be among the 10 best EU projects

related to Nanoscience)

Main technical and scientific impacts in the project are listed below. Future work in bold.

• Clear nomenclature for describing structure and magnetic properties of MNPs

and MNP ensembles

• Improvements in reproducibility of MNP synthesis. Over 50 new MNP systems were synthesized

in the project.

• Surveys of measurement methods for MNPs and their pros and cons, classification of these

methods including classification of different types of MNP systems

• A stakeholder committee group was formed in the NanoMag project that helped with the MNP

surveys performed

• Standard operation procedures, uncertainty budgets and metrological descriptions were developed

• Improved modelling of MNP magnetic properties, especially: dynamic magnetic behaviour

• Correlation analysis between MNP parameters determined by different analysis methods

• Over 80 new publications in international high impact journals and over 160 presentations and

seminars

Page 6: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

6

• E-learning modules (NPL-web site, linked from the NanoMag website). 132 people have already

enrolled to the first 2 modules. The number is expected to increase significantly when all modules

are launched after the end of the project.

• Substantial contribution to ongoing ISO MNP standards (ISO 19807 ” Nanotechnology — Liquid

suspension of magnetic nanoparticles — Characteristics and measurements', PG14

"Superparamagnetic beads for free cell DNA extraction)

• Analysis service in the future (information will be collected at NanoMag homepage and PTB

data server)

• Continuation with the MagnaStand EU project coordinated by Uwe Steinhoff (PTB).

• Round Robin measurements (same analysis methods but in different labs) using different types of

MNP systems

A detailed description of the results in each work package (WP) are given in the following sections.

WP1: Definitions of magnetic nanoparticles

Work undertaken

In WP1 we defined the MNP systems that were synthesized in WP3 and analysed in WP4. We will also

decide the additional commercial MNP systems that were analysed in WP2. The work was separated into

three parts:

• Definitions of single-core particles

• Definitions of multi-core particles

• Definitions of commercial magnetic nanoparticles

Scientific and Technical Results

3.1.2.1 Definition of single-core particles

In the initialization phase of the project, we have defined relevant parameters to be considered for

identifying particles as single-core MNPs. We have listed the main structural and magnetic characteristics

of single-core MNPs in D1.1. Single-core MNPs can be produced by several chemical methods. The main

routes are the aqueous phase and the organic phase synthesis techniques. An overview of the most

commonly used approaches both synthesis techniques has been prepared. As a result of this task, we

agreed on a list of single-core MNPs prepared by different synthesis routes with a variety of structural and

magnetic characteristics, and different surface modifications. Responsibilities and roles of the project

partners in synthesizing these MNPs were defined.

3.1.2.2 Definition of multi-core particles

The main structural and magnetic characteristic of multi-core MNPs were summarized in D1.2. An

overview has been compiled of multi-core MNP systems and their synthesis routes being appropriate to

produce MNPs for different applications such as magnetic hyperthermia, magnetic resonance imaging

magnetic particle imaging, magnetic separation and MNPs for bio-sensing and lab-on-chip platforms.

Based on this, we identified multi-core MNPs to be synthesized and characterized in WP3. The most

promising MNPs were selected for comprehensive analysis in WP4. We agreed on a list of multi-core

MNPs with magnetic cores from magnetite or maghemite, with small size distributions, iron oxide core

sizes in the range of 5 nm to 100 nm and hydrodynamic diameters below 100 nm or between 100 nm and

200 nm. The coating materials were dextran or carboxy dextran, starch, silica, polyethylene glycol or

corresponding polymer derivatives.

Page 7: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

7

3.1.2.3 Definition of commercial magnetic nanoparticles

We established a comprehensive survey on available commercial single- and multi-core MNPs based on

the information of the involved partners in WP1 (MICROMOD, NANOPET, SP, CSIC, ACREO, TUE,

UCL, PTB). In report D1.3, we compiled information available from internet product descriptions

published on companies’ websites. Four types of commercial players were identified: 1. Biomedical MNP

manufacturer and companies placing MNP on the market for in-vitro applications, 2. Medical in-vivo

injectable, 3. Technical engineering, and 4. Industrial chemicals supply. The project consortium decided to

work with focus on biomedical commercial MNP according to Type 1. Six commercial MNP systems

were defined for further analysis. Four of them are single- and multi-core MNPs with hydrodynamic

diameter below 100 nm and different magnetic relaxation behaviour at room temperature, and two

samples with larger particle size for magnetic separation and micro-sensing applications.

Impact on other Work Packages

The defined single- and multi-core MNPs were synthesised and initially characterized in WP3. The MNPs

were utilized in our comprehensively studied in WP4 in order to improve and re-define the analysis

methods. The defined MNPs were also used for our application and benchmark activities in WP6. The

defined commercial MNPs were characterized in WP2 in order to decide which analysis technique and

which models will be used in WP4 and which MNP parameters can be obtained.

WP2: Definitions of analysis methods

Work undertaken

In this work package, we have used the commercial single- and multi-core MNPs defined in WP1 for an

initial characterization using various analysis technique. We have investigated the analysis techniques and

decided which techniques we use in WP4 for the respective MNP system and which nanoparticle

parameters were important for our standardization work in WP5. We have also studied which models are

needed in order to determine relevant parameters for a deeper understanding of the MNPs. The work was

divided into three parts:

• Analysis of the initial measurements

• Definition of characterization and analysis methods

• Definition of models

Scientific and Technical Results

3.2.2.1 Analysis of the initial measurement

A comprehensive overview (D2.1) has been prepared which comprises the structural and magnetic

parameters of the commercial MNPs that we have defined in WP1. Here, we summarized the results

obtained by the available analysis techniques in NanoMag. The parameters of the following commercial

particle system were summarized:

• Micromod BNF multi-core particle with a hydrodynamic diameter of 80 nm.

• NanoPET FeraSpin-R multi-core particle system with a hydrodynamic diameter of 60 nm.

• Ocean Nanotech SHP25 and SHP20 single-core particles with hydrodynamic diameters of 25 nm and 20 nm

respectively.

Along with the results of the characterization of the particle system, the overview D2.1 comprises for each

analysis technique and based on the analysis results, a summary of the standard practice measurements

including information on the sample preparation and amount, used concentrations, details on measurement

systems and parameters, measurement time, calibrations and used models for data analysis. From these

information, a measurement matrix has been generated which is shown in Table 1. It gives a summary of

Page 8: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

8

the analysis techniques that are available in NanoMag and the accessible structural and magnetic MNP

properties.

Table 1: Overview of the analysis methods and accessible MNP properties

1 Scherrer analysis can yield the average crystal coherence length, but not the particle distribution. 2 only EA can be determined;

If the anisotropy constant is known, the particle volume can be derived. 3 The concentration can be determined by e.g. ICP-MS,

prussian blue staining or phenanthroline. 4 By investigating a concentration series. 5 The energy absorption can be estimated

from by analysis of χ’’. (X) = Derivable under favourable circumstances, e.g. if dp >> resolution limit of the microscope

Page 9: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

9

3.2.2.2 Definition of analysis methods and models In the definition stage in WP2, a survey was compiled based on information on the data analysis, the structural and

magnetic parameters that can be determined, assumptions or additional input parameters for the data analysis and a

discussion on possible uncertainties and their magnitude. The survey further comprises information on interrelation

with other analysis methods, proposals for measurement improvement and modifications for more reliable output

parameters and modelling and simulations for the interpretation of measurement results.

Based on this survey the analysis methods were classified to:

Group 1: Structure, chemical composition and particle size distribution

• Conventional scattering techniques (XRD, ND)

• Small-angle scattering (SAXS, SANS)

• Electron microscopy (SEM, TEM)

• Dynamic light scattering (DLS), electrophoretic light scattering, zeta-potential

• Asymmetrical field flow fractionation (AF4)

• Inductively Coupled Plasma Mass Spectrometry (ICP-MS)

• Mössbauer spectroscopy

Group 2: Temperature and field dependent magnetization and resonance measurements

• Magnetization versus temperature (m vs. T)

• Isothermal magnetization measurements (m v H)

• AC susceptibility vs. temperature (AC v T)

• Ferromagnetic resonance (FMR)

Group 3: Frequency and time dependent magnetization/relaxation measurements

• Magnetorelaxometry (MRX)

• Frequency dependent AC-susceptibility (ACS)

• Magnetic particle spectroscopy (MPS)

• Rotating magnetic field method (RMF)

Group 4: Application oriented magnetic measurements

• NMR T1- and T2-Relaxivity

• Magnetic Separation

• Magnetic Hyperthermia

• Brownian relaxation measurements using on-chip relaxometry using a magnetoresistive sensor and

optomagnetic sensing

Models were defined for those analysis techniques where modelling is needed to extract the MNP

parameters from the measurement data.

Impact on other Work Packages

The results of the initial characterization were used in WP3 for the comparison of commercial MNPs and

new synthesized single- and multi-core MNPs. The identified chemical, structural and magnetic

characteristics that can be determined by our defined methods and models were studied in WP4 for the

characterization of new synthesized MNPs. We continuously improved our analyses and assess our

definitions within WP4 which provided the scientific background for our standardization work in WP5.

Page 10: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

10

WP3: Magnetic nanoparticle synthesis

Work undertaken

In this WP we have synthesised magnetic single-core and multi-core particles with special magnetic,

chemical and structural properties according to the definitions in WP1 and we used these MNPs for our

analysis work in WP4 in order to define the analysis standard techniques in the standardization method

work in WP5. We also used commercial magnetic nanoparticles for the comparison with the new

synthesized MNPs.

Scientific and Technical Results

We have identified different synthesis routes susceptible for being standardized for the production of

single- (task 3.1) and multi-core (task 3.2) magnetic nanoparticles suspensions for biomedical applications

(Milestone MS3), according to the definitions in WP1.

Commercial nanoparticles were chosen from a broad range of manufacturers and suppliers marketing

nanoparticles. The quantity and quality of information provided varies significantly between. The

comparison of different commercial with new synthesized nanoparticles (WP2) was challenging and not

feasible without their in-house characterization (task 3.3). For example, the Fe concentration provided by

the manufacturer, which was critical for WP2, was not reliable and differed significantly from the actual

measured values. Consequently, we elaborated a report describing the best way to determine the Fe

concentration in those suspensions to assure uncertainty below 3%.

The resulting samples have been characterized by particle size, hydrodynamic size, Fe concentration,

osmolality, pH, zeta potential and dispersion stability (task 3.4) and they have been compared with

commercial samples selected in WP1 (task 3.3, D3.3). Only those having long-term colloidal stability

(months) were distributed to WP4 and WP6 (D3.1 and D3.2) and a technical data sheets was designed.

We have developed standard operating procedures (SOP), describing the synthesis and surface

modification of these iron oxide magnetic nanoparticles to obtain colloidal suspensions in water at pH 7

following recommendations from WP5. Second batches of single-core (D3.4) and multi-core particles

(D3.5) prepared following these SOPs were delivered to WP4 and WP6.

We have analyzed the reproducibility of the selected synthesis methods and the inter-lab reproducibility

based on the characterization results provided by WP4. The SOPs have been extended including more

details on the experimental procedures and finally, non-expert labs have been invited to carry out the

synthesis following the extended SOPs (work in progress).

We have analysed the key parameters controlling particle size, aggregation and colloidal stability.

Analyses of the mechanism of particle formation and degradation have also been done in order to improve

reproducibility and reaction yield.

A tight collaboration has been stablished between synthesis groups in WP3 for improving the synthesis of

magnetic nanoparticles and its dispersion in water. Samples produced in this WP present high uniformity,

good crystallinity, long term stability and good control of core, particle and hydrodynamic size, better than

most of the commercial samples.

3.3.2.1 Selected MNP samples

Single-core particles

Magnetic nanoparticles with very low polydispersity (<10%) have been synthesized by high temperature

decomposition of iron oleate and they have been coated with silica via microemulsions (Sample CSIC01)

and dimercaptosuccinic acid, DMSA (Sample CSIC12) leading to single core particles (Fig. 1A). Silica

and DMSA were chosen for the coating since they are well‐studied materials, easily functionalizable and

biocompatible. Silica and DMSA has been chosen for the coating since it is a well‐studied material, easily

Page 11: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

11

functionalizable and biocompatible. The synthesis and coating methods were optimized to control the

particle size and coating thickness (Fig. 1B).

Other method that was explored to obtain single core particles without size selection was this involving

the synthesis of antiferromagnetic precursors which were subsequently coated with silica and reduced to

magnetite without change in morphology. Cores with different morphology were obtained (Fig. 1C). First,

this approach has the advantage of low inter-particle interactions of as-synthesized antiferromagnetic

nanoparticles. Moreover, it covers different core size ranges and allows obtaining different morphologies

such as rhombohedra (CSIC09), discs or needles below 200 nm [4].

The synthesis and coating methods were optimized to control the particle size and coating thickness. On

the other hand, cores with different morphology have been synthesized from antiferromagnetic precursors

which were subsequently coated and reduced to magnetite without change in morphology. Examples of

different core size from 12 to 20 nm, same coating thickness, different coating thickness from 14 to 24

nm, same core size 16 nm and different morphology, same silica coating, can be seen in figure 1 (A-C)

below.

Silica DMSA

Fig. 1. A) Single core particles with different core size from 10 to 20 nm and same coating thickness,

silica on the left and DMSA on the right.

Fig. 1 B) Single core particles with different silica coating thickness from 14 to 24 nm and same core size

16 nm.

Fig. 1 C) Single core particles with different morphology and same silica coating.

Multi-core particles

Controlling number of cores per aggregates, same core size

BNF-Starch particles with nominal diameters of 80 nm and 100 nm were selected as commercially

available multi-core particles from Micromod in WP1. Within WP3 Micromod followed different

strategies to modify the coating process of the iron oxide cores of BNF particles (around 20 nm core size)

Page 12: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

12

to change the number of cores per aggregate and to obtain particles with a more uniform number of iron

oxide crystals per particle to improve the magnetic particle properties (Table 1). Magnetic fractionation

techniques and the peptization of iron oxide cores before coating led to a smaller and more uniform

number of iron oxide cores per particle.

Table 1. Summary of multi-core particles derived from iron oxide cores of BNF particles.

MM-03 MM-04 MM-05 MM-06

Core material -Fe2O3/Fe3O4 -Fe2O3/Fe3O4 -Fe2O3/Fe3O4 -Fe2O3/Fe3O4

Coating material dextran dextran starch Poly(acrylic acid)

Na salt

Functional groups OH OH OH COOH

PCS size

(Z-Average) 79 nm 64 nm 115 nm 126 nm

PDI 0.06 0.10 0.08 0.12

Fe concentration 5.0 mg/ml 5.0 mg/ml 5.0 mg/ml 5.1 mg/ml

Comments

Magnetic

Fractionation (planar

design)

Peptization of iron

oxide before coating

Magnetic Fractionation

SEPMAG-Q100 [2]

Peptization and

coating in one step

The commercial and biocompatible sample FeraSpin R, which is synthesized by aqueous coprecipitation

of Fe(II) and Fe(III) in the presence of carboxydextran as stabilizing agent, consists of clustered 5 nm iron

oxide nanoparticles forming aggregates of various sizes (Fig. 2). Via magnetic fractionation different

narrowly distributed size fractions of these aggregates were obtained by NanoPET, while all aggregates

are composed of the same sized cores having a diameter of about 5 nm. From these the smallest size

fraction FeraSpin XS, containing solely single-core particles, and a medium size fraction FeraSpin L were

chosen for an extensive characterization in WP4.

Fig. 2. TEM images of a cluster of FeraSpin XS (5 nm cores coated with carboxidextran) at different

magnification and hydrodynamic size evolution of FerraSpin samples with the magnetic fractionation.

Controlling core-core interaction

Different strategies to obtain flower-shaped iron oxide assemblies in the size range 25-100 nm were

examined (Fig. 3 A). The routes are based on the partial oxidation of Fe(OH)2, polyol mediated synthesis

or the reduction of iron acetylacetonate. The nanoparticles are functionalized either with dextran or citric

acid and their long-term stability is assessed. Key synthesis parameters driving the self-assembly process

capable of organizing colloidal magnetic cores into highly regular and reproducible multi-core

nanoparticles were determined. This is the first step towards standardized protocols of synthesis and

characterization of flower-shaped nanoparticles.

Page 13: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

13

Fig. 3 A) Multicore samples with magnetic cores of around 10 nm self-organized forming larger

nanoparticles of around 30 nm up to 150 nm (NPG3310, MM08, CSIC10, SP06) [1].

Different core size, same particle size

The polyol-mediated synthesis has been explored and developed for the preparation of well-controlled

magnetic nanoparticles with different core size and arrangement to form the final multicore particles. A

prolonged heating of the flowers (nanoflower nanoparticles) leads to particles with larger cores with

interesting magnetic and colloidal properties (Fig. 3B).

Fig. 3 B) Multicore nanoparticles prepared by the polyol process with different core size depending on the

heating time, from 2 h up to 48 h [2].

Different coating

In order to have a broad portfolio of different nanoparticles covering a wide range of physical and

magnetic properties, several other synthesis techniques and coating materials were utilized [11-14].

NPG3310 for example was synthesized by a partial oxidation pathway and coated by the biocompatible

polymer dextran, inducing a steric stabilization (Fig. 3C). By using citric acid and coprecipitation, charge

stabilised nanoparticles have been synthesized. Nanoparticles, being stabilised sterically and by charge,

have been synthesized by using poly(acrylic acid) as coating material.

Fig. 3 C) TEM micrographs of dextran-, poly(acrylic acid)- and citrate stabilized multi-core samples synthesized by

nanoPET.

Page 14: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

14

Flower like particles of 100 nm core sizes have also been coated with dextran, citric acid, amino propyl

silane (APS) and amino dextran with interesting colloidal properties and different surface charge, going

from positive (+42 mV) with animodextran to negative (-30 mV) with citric acid and Z average sizes

around 200 nm.

Different super-structure

SP synthesized nanoflowers (SP06) by means of sodium borohydride, which acts as reducing agent of iron

(III) acetylacetonate (Fe(acac)3). Nanoflowers synthesized by this route were embedded on polystyrene

spheres via the emulsion solvent evaporation (ESE) process or encapsulated forming super-structures. The

differences in nature of aggregation of the magnetic cores could lead to different modes of inter-particle

magnetic interactions. This would have an impact on application oriented properties such as NMR

relaxivities, hyperthermia etc.

Fig. 3 D) Multicore MNPs with different modes of magnetic core aggregation (left: SP06 and right: SP07).

Interesting series from single- to multi-core MNPs

Interesting series of magnetic suspensions going form multicore to single core nanoparticles were obtained

with particles made of 5 nm cores by NanoPET as mentioned before (FeraSpain samples) and for 30 and

60 nm cores prepared by ICMM [15] and Micromod by magnetic fractionation after dextran coating

(CSIC04, 5, 6) and sedimentation fractionation after PAA-Na coatings with different molecular weights

(CSIC08) (Fig. 4A). We observed excellent reproducibility of CSIC05 and CSIC04.

Single-core and multi-core, including hollow spheres and nanoflowers, can be prepared by the polyol

process (Fig. 4B). Sodium acetate (NaAc) can control the nucleation and assembly process to obtain the

different particle morphologies that can be further stabilized in water by coating with citric acid. The

particles are formed by burst nucleation and growth processes that determine the final nanostructure [2].

Finally, by controlling the internal structure of anisometric particles [4], we have developed single and

multicore particles as those presented in Fig. 4C. The possibility of generating a discontinuous structure

within a particle by forcing the pore formation may be an interesting strategy to develop new materials

with tuned magnetic properties for biomedical applications.

A NP@DEXTRAN CSIC-05-B CSIC-04-B CSIC-06

0

20

40

60

80

100

120

140

160

180

200

Z a

ve

(n

m)

Sample Name

Z-average (DLS)

Aggregate diameter (TEM)

Page 15: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

15

B

C

Fig. 4. A) From multicore to single core nanoparticles 30 nm cores coated with dextran (right-top and

bottom, CSIC05-CSIC04-CSIC6) and subjected to magnetic fractionation. B) Single-core and multi-core

(hollow spheres and nanoflower) prepared by the polyol process (DEG/EG). C) Needle shaped magnetic

nanoparticles with different internal structure.

Multi-core nanoparticles prepared in different polyol media (DEG/EG) and in the presence of different

reactants such as NaAc and NMDEA that modify the viscosity and the boiling point of the media [5], [6].

Impact on other Work Packages

The single- and multi-core MNPs synthesized in WP3 were characterized in WP4 and WP6.

Synthesized particles with defined properties were used in WP4 to verify, improve and harmonize the

analysis methods to be standardized in WP5.

WP4: Magnetic nanoparticle analysis

Work undertaken

In WP4 we carried out the characterization and analysis work and we used the analysis methods and

models that were defined in WP2. We have classified the analysis methods according standard methods

that were used for all MNP samples and more specialized methods used for selected MNP systems. We

studied single- and multi-core MNPs that were synthesized in WP3 and we compared our results with

commercial MNP systems. We correlated the results obtained by different analysis techniques in order to

get a self-consistent picture of the MNP systems. The work was divided into four parts:

• Characterization and analysis results from the single-core nanoparticles

• Characterization and analysis results from the multi-core nanoparticles

• Finely tuned characterization and analysis methods for the single-core and multi-core nanoparticles

• Correlation between analysis techniques

Scientific and Technical Results

Terminology for magnetic nanoparticles

A clear terminology for describing the structural and magnetic properties of single- and multi-core MNPs

and MNP ensembles has been developed and published in [7]. Here, we also considered those definitions

for MNPs that are available in existing standard documents. Such a summary of definitions of the MNP

Page 16: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

16

components was essential for comparing the results among the project partners and among different

measurement techniques, and it is indispensable for a coherent standardization structure MNP samples.

Classification of magnetic nanoparticles

The outcome of our characterization work in WP4 led to a classification of nanoparticles according to

their number of cores inside a particle which leads to differentiation in single- and multi-core MNPs, and

we reviewed different approaches for the synthesis of these MNP systems [8]. Both particle systems are

shown in Figure 1. Single-core MNPs contain one magnetic core per particle and the core is covered by a

matrix to prevent aggregation and agglomeration. In multi-core MNPs several cores exist within the

matrix forming an individual unity.

Figure 1: Schematic diagram of a single- (left) and a multi-core (right) MNP, taken from [7].

The arrangement of cores within a MNP sample has significant influence on the magnetic properties.

Whereas in single-core MNPs in suspension the magnetic moment of the particle cores can rotate via Néel

and Brownian rotation, in multi-core MNP systems Brownian rotation is suppressed as the cores are

anchored in the matrix. Only Brownian rotation of the entire particle is allowed in this system. In addition

to that, for describing the static and dynamic magnetization behavior, magnetic interaction between the

cores in multi-core structures may become relevant if the cores are closely packed. This led to the concept

described in [9], where we classified MNP systems according to their magnetic relaxation properties and

particle size parameters which are determined by utilizing magnetic analysis techniques such as ACS or

MRX and techniques like TEM and DLS capable to probe the core and particle size and the hydrodynamic

size.

The complex inner structure of multi-core MNPs lead to unique magnetic properties and can explain for

example their high performance in magnetic particle imaging [10], [11] or other biomedical applications

[12]. This shows that especially multi-core MNPs needed a comprehensive characterization and a careful

interpretation of structural and magnetic parameters including the correlation of different MNP

parameters.

Page 17: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

17

Figure 2: Schematic picture of two subclasses of multi-core MNPs

The so-called flower-shaped MNPs [13] or “nanoflowers”, as a special type of multi-core MNPs, have

been intensively studied within WP4. These multi-core particles consist of clusters of strongly coupled

cores which exhibit unique magnetic properties and thus they are potentially relevant in for example

magnetic hyperthermia. Figure 2 shows the nanoflowers along the multi-core MNPs with relatively weak

coupling between the cores. The focus of the characterization work was on the exploration of interaction

between the nanocrystals inside an MNP. Thus, in [1] we classified the flower-shaped MNPs according

their interaction between the cores and between the particles which can be adjusted by different synthesis

routines. This enables us to tune the static and dynamic magnetic properties of MNPs for specific

applications.

3.4.2.1 Classification of analysis methods

A classification of analysis methods into standard and advanced analysis techniques has been created and

published in [14]. Standard techniques have large potential for standardization, whereas more advanced

methods that provide additional information in order to gain a more detailed picture of an MNP system,

however, due to their complexity and availability, these methods have limited potential to pose as standard

methods for MNP characterization. Partners of the NanoMag consortium being experts in the field of

nanoparticle research have assessed the analysis techniques considering different scientific, technological

and economic aspects [14].

We furthermore developed a measurement matrix which provides information on the sample requirements

(amount and sample forms) for each analysis technique and we gave an overview of the estimated cost of

a single measurement using the technique and the types of sample, the method should be applied to.

Table 2 presents the outcome of the assessment of analysis methods as a classification into standard

methods, advanced methods and intermediate methods. The latter could potentially serve as standard

methods; however, their results have to be correlated with those obtained by other techniques. Note that

some methods belong to several categories (e.g. Mössbauer and ND providing both structural and

magnetic information). Detailed information on assessment of analysis methods have been published in

[14] and in our report D4.1.

The results of this task had consequences for our subsequent analysis work as we used the standard

methods for the characterization of all NanoMag samples, whereas the advanced methods are used to gain

a deeper understanding of selected MNP systems. Furthermore, we have identified for our standardization

work in WP5 a selection of commonly used techniques, which should undergo a standardization process

with respect to the properties of MNPs. The experience from the present analysis of characterization

methods for MNP provided valuable arguments in ongoing formal ISO standardization processes.

Page 18: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

18

Table 2: Result of assessment of methods

Standard

method

Intermediate

method

Advanced

method

Structure, composition,

size

DLS, SEM, TEM, AF4,

SAXS, ICP-MS XRD, Mössbauer XAFS, ND, SANS

Magnetic properties DCM, ACS vs. f,

ACS vs. T

FMR, MRX, MPS, RMF,

Mössbauer ND, SANS

Application oriented

methods

MPS, NMR

magn. Separation,

magn. Hyperthermia,

Chip-ACS

3.4.2.2 Characterization and analysis results from the single-core MNPs

Our report D4.2 provided a detailed description of the structure and the magnetism of single-core MNPs

and MNP ensembles and we pointed out that only a few measurement techniques are available which

provide information on a single nanoparticle. The majority of techniques measure the properties of an

MNP ensemble and in the simplest case, the MNPs can be considered to be identical. However, in

practise, the MNPs exhibit some distribution of parameters, e.g. for MNP size, magnetic moment,

magnetic anisotropy, etc. Here often a certain functional form for the probability density function in the

model is assumed and is most cases a lognormal distribution is used. An alternative to that is the

regularized inversion method which we have developed and published in [15]. The main advantage of the

numerical inversion method is that no ad hoc assumptions regarding the line shape of the extracted

distribution functions are required. This approach has been verified by comparing the results with the

results obtained by standard model fits, i.e. where lognormal distribution was assumed.

Along with the basic description of single-core MNPs and ensembles our report D4.2 gave comprehensive

summary of analysis methods and models for single-core MNP description. The information on each

analysis techniques are summarized according the metrological checklist [16] which provides a guideline

for the development of a standard. We furthermore presented an overview of the results of structural and

magnetic characterization of single-core MNPs which have been synthesized within the project. As a

consequence of the variety of analysis methods, there is some redundancy in parameters which helps one

to verify and refine models. In [17] we have published the results of the comparison of single-core MNP

sizes determined by different non-magnetic and magnetic analysis techniques. It was found that the mean

core diameters determined from TEM, DCM, ACS and MRX measurements agree well although they are

based on different models. We found good agreement among the results which proved the applicability of

these techniques and their related models for the characterization of single-core nanoparticles. In a similar

study, we found for single-core MNPs also very good agreement between core diameter obtained by TEM,

DCM and MRX [18]. However, it turned out that in the investigation of multi-core MNPs large

differences were present mainly caused by the applied models and the complex core structure.

In [4] we correlated structural and magnetic properties of large single-core MNPs using a variety of

analysis methods was published in. We could demonstrate how the magnetic behavior is affected by the

shape of the MNPs, their internal structure and the reduction process.

We could demonstrate in [19] that measurements of the complex susceptibility as a function of frequency

on suspensions of thermally blocked MNP allow the simultaneous estimation of the hydrodynamic size

and of the effective anisotropy constant.

The magnetic field dependence of the Brownian and Néel relaxation has been investigated using two

single-core MNP systems [20]. Here we have shown that we are capable to model the dynamic magnetic

behavior as a function of field amplitude and under application of an ac field superimposed by a static

magnetic field.

Page 19: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

19

In [21] the micro- and mesostructure of self-assembled mesocrystals composed of nanocubes with

different edge lengths in the absence and presence of an applied magnetic field has been investigated. The

results of this study are summarized in a qualitative phase diagram which outlines the preparation of

mesocrystals and arrays with tunable micro- and mesostructure.

3.4.2.3 Characterization and analysis results from the multi-core MNPs

In our report D4.3 we presented a detailed description of the inner structure and the magnetism of multi-

core MNPs. As in most cases interactions between the cores inside a nanoparticle must be considered for

describing the magnetism of multi-core MNPs, we gave a detailed description of the magnetic interaction

and relaxation properties on the basis of multi-core and flower-shaped MNPs. Report D4.3 also presented

a comprehensive survey on the structural and magnetic properties of a selection of four multi-core MNPs

that have been synthesized in our project. We summarized here information on each analysis techniques

and models in accordance to the metrological checklist [16] and we considered particularities which arise

from interactions in multi-core MNPs.

We were able to disclose the distribution of cores inside the MNPs and we could explain the magnetic

behaviour which is significant affected by dipolar interactions between the cores [22]. Therefore, we

studied the structural and magnetic properties of multi-core MNPs using a generalised numerical inversion

technique.

In [23] we could show on the commercial FeraSpin series synthesized by nanoPET that FeraSpin XS can

be described as individual nearly spherical single-core MNPs, while FeraSpin L consists of larger, slightly

elongated clusters in which the interaction between the cores significantly alters the magnetic properties.

We comprehensively studied flower-shaped MNPs diverting core sizes and different packing densities

inside a particle and thus variating interactions [1]. By comparing the results obtained from various

analysis methods, we could disclose the inner structure of the core-clusters and link them to their magnetic

properties. The heat generation of the flower-shaped MNPs in different stages of the synthesis was

determined in [2] and compared with other particle types.

We explored the effect of the alignment of the magnetic easy axes on the dynamic magnetization of

immobilized multi-core MNPs under an AC excitation field [24] and we obtained quantitative agreement

between experiment and simulation. These results indicate that the dynamic magnetization of immobilized

MNPs is significantly affected by the alignment of the easy axes.

Characterization of multi-core MNPs with application oriented methods

Large effort has been made in characterizing multi-core MNPs with application oriented methods with the

aim to link the structural and magnetic characteristic and their performance in final application. We could

show for example, how the amplitude and shape of the MPS spectra is affected by different physiological

media [25]. Additionally, the observed linear correlation between MPS amplitude and shape alterations

can be used to reduce the quantification uncertainty for MNP suspended in a biological environment.

In [26] we proposed a dual-frequency acquisition scheme to enhance sensitivity and contrast in the

detection of different particle mobilities compared to a standard single-frequency MPI protocol. The

method takes advantage of the fact, that the magnetization response of the tracer is strongly frequency-

dependent, i.e. for low excitation frequencies a stronger Brownian contribution is observed.

In [27] we studied the structure and the magnetism of MNPs that were synthesized by a promising

diffusion-controlled synthesis. From the characterization, we could demonstrate that a diffusion-controlled

synthesis approach process allows to produce MNP suspensions with a large fraction of particles

exhibiting a mean effective magnetic core size of about 28 nm which lies within the size range considered

ideal for MPI.

We revealed how the particle size and concentration have influence on the separation of multi-core MNPs

[28]. It was found that an increasing particle concentration leads to a reduction of the separation time for

large nanoparticles due to the higher probability of building chains. For smaller MNPs the chain-formation

is suppressed due to faster thermal fluctuation which led to concentration-independent separation times.

Page 20: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

20

In [29] we explored the suitability of multi-core-MNPs in different polymer matrices to be used in MRI

and we compared the MNPs with a MNP system approved for clinical use as contrast agent. Along with a

comprehensive structural and magnetic analysis we could show that the synthesized MNPs exhibited

higher R2 relaxivities and R2/R1 ratios compared to the commercial MNPs indicating their potential as

new MRI contrast agents.

The effect of nanoclustering and dipolar interactions on the efficiency in magnetic hyperthermia was

analyzed in [30]. We have shown that the magnetic hyperthermia performances of nanoclusters and single

nanoparticles are distinctive and that nanoclustering of particles with randomly oriented easy axes is

detrimental to the SAR. A decrease in ILP is observed when the nanocluster size and number of particles

in the nanoclusters increase. This result is very interesting as in nanoflowers, where the cores inside the

particles exhibit the same crystalline orientation, the SAR increases with increasing cluster size. For the

individual MNPs, the SAR depends on particle concentration and thus increasing dipolar interaction.

We explored ellipsoidal MNPs subjected to an external AC magnetic field. First, the heat release is

increased due to the additional shape anisotropy [31]. The rods can also dynamically reorientate

perpendicular to the AC field direction. Importantly, the heating performance and the directional

orientation can be controlled by changing the AC field treatment duration, thus opening the pathway to

combined hyperthermic/mechanical nanoactuators for biomedicine.

3.4.2.4 Finely tuned characterization and analysis methods for the single-core and multi-core

nanoparticles

The interaction among the NanoMag partners allowed to synthesize series of MNPs with varying

structural and magnetic parameters. These model MNPs have been used to verify and to improve our

analysis methods and the physical models.

Measurements on MNP series

As described in our report D4.4, a characterization strategy has been developed for MNPs which consist of

the identical cores but different assembly size, with the aim to provide a consistent procedure for

standardized analysis of multi-core nanoparticles. Along with a comprehensive structural and magnetic

characterization we could show that the number of cores inside a MNP has significant influence on the

heat generation in magnetic hyperthermia.Alongside other analysis techniques we utilized FMR and AF4

to derive a comprehensive understanding of the FeraSpin series synthesized by nanoPET [23]. We could

disclose the coupling between the cores and we could show that FeraSpin R can be described as a

superposition of the size fractions FeraSpin XS and L.

Verified and improved analysis methods

In [32] we demonstrated that improved SAXS in combination with SLS measurements delivered estimates

of these morphological parameters and this information can then be transferred into a mean core distance

inside the multi-core structure.

In [33] we could prove that ACS is capable to simulate the dynamic magnetic response of a sample

possess a bimodal size distribution, proposed that the two particle sizes result in sufficiently deviating

time constants. The numerical approach is more reliable when one particle fraction relaxes via Néel and

the other via Brownian mechanism. Using Monte Carlo simulations for fitting the SAXS, we are also able

to resolve the bimodality in the particle size. This result is important since only a few methods that can be

used to dissolve a size distribution with more than one fraction.

The dependency of the Brownian and Néel relaxation times were studied by ACS as a function of

frequency and field amplitude [20]. It was found that the Néel relaxation time decays much faster with

increasing field amplitude than the Brownian one. Whereas the dependence of the Brownian relaxation

time on the ac and dc field amplitude can be well explained with existing theoretical models, a proper

model for the dependence of the Néel relaxation time on ac field amplitude for particles with random

Page 21: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

21

distribution of easy axes is still lacking. These findings are of great importance of applications where

larger magnetic fields are used, e.g. MPI and magnetic hyperthermia.

In [34] we presented a new experimental approach to characterize an MNP system with respect to

quantitative MRI. We could show that the hydrodynamic fractionation by AF4 and the subsequent

structural and magnetic characterization of the size fractions by DLS, MALS, MPS and NMR enables us

to evaluate the suitability of a MNP system for quantitative MRI and verify the theoretical predictions for

the size dependence of relaxation rates at the same time. The approach could facilitate the choice of MNPs

for quantitative MRI and helps clarifying the relationship between size, magnetism and relaxivity of

MNPs in the future.

Along with the numeric inversion method presented above, we have developed a new method based on the

iterative Kaczmarz algorithm that enables the reconstruction of the size distribution from magnetization

measurements without a priori knowledge of the distribution form [35]. We concluded that this method is

a powerful and intuitive tool for reconstructing particle size distributions from magnetization

measurements. We have also used the Kaczmarz' algorithm for the determination of hydrodynamic size

distribution from MRX measurements and we could show that this method is able to determine the

hydrodynamic size distribution in agreement with either the known input distribution, in the case of

simulated data, or other size estimates determined with different methods such as thermal magnetic noise

spectroscopy and dynamic light scattering in the case of measured data [36].

In [37] we could identify the similarities and the differences in MRX and thermal magnetic noise

spectroscopy. Both techniques are based on the same physical principle, i.e. the thermal

fluctuations of the magnetic moment.

A new MPS setup was built which allows temperature dependent measurements in order to investigate the

temperature dependence of the harmonics spectra [38].

Standard operation procedures

In preparation of our standardization work in WP5, Standard Operating Procedures (SOPs) for each

analysis methods have been developed within WP4. For analysis methods being available at different

facilities, a harmonized standard operation procedure has been compiled. The SOPs were published in our

report D5.2. On the basis of the prepared SOPs, we have performed Round Robin tests, where we

compared the MNP parameters measured by different partners. The results of these comparison studies

were utilized to continuously improve the SOPs and to identify influence factors that were relevant for

discrepancies among the results. However, within the project duration we were not able to finish our

studies and to measure identical values at different institutes. This is still a challenge for future research

projects.

Uncertainty budget calculation

In a Mössbauer study [39], we were able to identify independent influence factors that are relevant for the

uncertainty of the mean isomer shift, used for the quantification of the magnetite content in MNPs, and we

could derive a quantitative expression for the uncertainty budget. This concept has been applied at two

different laboratories where the magnetite fraction values determined from the Mössbauer measurements

agree within their respective uncertainties. This activity served as a model project for other analysis

techniques in order to develop an uncertainty budget for all derived structural and magnetic parameters

that are relevant for the reliable characterization of MNPs. Within the project we could identify the main

influence factors for uncertainty for most of the analysis methods, however, we could not achieve the

preparation of uncertainty budgets for all techniques. This should be solved in future research projects, for

instance the newly started MagNaStand project in July 2017, coordinated by PTB where some of the

NanoMag partners are participating (PTB, RISE Acreo, UCL, Micromod) as well as new partners from

both industry and metrological institutes.

Page 22: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

22

3.4.2.5 Correlation between analysis techniques

The comparison of MNP parameters is of utmost importance in order to get a self-consistent description of

MNP systems. Consequently, we correlated our results in most of our activities. Our public report D4.5

gives an overview of the main results of a) correlation between the same MNP parameter determined by

different techniques and b) the comparison of different MNP parameters. A consistent picture was found

for the hydrodynamic particle size. However, quite some scatter between data was observed for core

parameters, such as core size, effective anisotropy constant, and magnetic moment.

It was found that for single-core nanoparticles a number of methods consistently provide the same value

for the core size and hydrodynamic size distribution. Slight differences can be attributed e.g. to the applied

models. The situation is somewhat more complicated for multi-core MNP and nanoflowers.

Although there is a variety of analysis methods e.g. for determining the core size (TEM, DCM, MRX,

ACS, SAXS, etc.), there is no best method which could be identified as standard one. However, the good

agreement of size parameters, found when comparing techniques applied to the same sample, indicates

that basically any of the methods can be applied.

The estimation of the effective anisotropy constant K remains an open task. Although a number of

magnetic methods provide information on K, the physical background is manifold, ranging from the

determination of the anisotropy energy via the Néel relaxation time to the intra-potential-well contribution

in the dynamic susceptibility and the blocking temperature. A major problem for estimating the anisotropy

constant applying the various methods is that all techniques require their very specific nanoparticles.

A remaining challenge for future research will be a better understanding of the effective parameters and

their correlations for multi-core MNP and nanoflowers.

Impact on other Work Packages

The results and the finding in this work package have been utilized in WP3 for the improvement of MNPs

and to synthesize MNPs with specific properties.

The scientific results of our work on the classification of MNP and the classification of analysis methods

have been used in our standardization work in WP5.

The characterization of single- and multi-core MNPs has been utilized to harmonize and to improve the

analysis methods. The correlation of results led to a better understanding of link between the structural and

magnetic properties of MNPs. As a consequence, our achievements were relevant in the standardization

work in WP5 and it provided the technological background for our cooperation in the ISO/TC 229.

The partners in WP4 have provided the technical and scientific content for the preparation of a SOP for

each analysis technique considering the mandatory elements of the metrological checklist. This work was

important for WP5 as standard operation procedures are an essential step toward a standardized MNP

characterization. Furthermore, the development of uncertainty budgets was crucial for our standardization

work

The extracted structural and magnetic properties were relevant in WP6 for the verification and

improvement of application measurements.

WP5: Standardization of magnetic nanoparticles

Work undertaken

In WP5 we studied the results from the synthesis work in WP3 and the analysis result of WP4 obtained on

new synthesized and commercial MNPs and we have defined standardization methods and parameters.

The work was divided into three parts:

• Standardization strategies of magnetic nanoparticle systems

• Defined standardization methods and relevant parameters

• Standardization roadmap

Page 23: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

23

Scientific and Technical Results

3.5.2.1 Standardization work strategies

Our report D5.1 presented an overview of the identified key physical parameters and the defined

terminology to be used for classification and description of magnetic nanoparticle systems. This overview

represented the state-of-the-art in science and technology which can be found in literature considering also

existing standards and our knowledge we gained in WP4.

We further summarized commonly used analysis techniques for the characterization of MNPs. Here, we

have drawn together the information contained within existing reports submitted by the NanoMag

partners, and to structure it in a manner similar to the requirements listed within the ISO/IEC directives for

the drafting of international standards.

We gave an overview of existing standardization work on sampling definitions, characteristics and

measurements relating to MNPs, labelling, MNP manufacturing and on standard reference material for the

MNP characterization. Finally, the standardization work strategies report D5.1 contained information on

the current and future need for metrology of MNPs.

The main results of this task have been published in [7]. Along with a summary of the state-of-the-art in

MNP science, the paper represents significant opportunities for future research projects, and are intended

to provide an overview or roadmap of major topics which should be addressed within the coming years.

This work is intended to act as a precursor to the future development of MNP standards. The

standardization work and result are also reported in D5.2 (Defined standardization methods and relevant

parameters) and D5.3 (Standardization road map).

A result of this activity is shown in Figure 3, a mix-and-match approach as a combinatorial map showing

the suggested structure around which standards relating to MNP suspensions may be built. Underlying all

of the other document types are the vocabulary standards and materials specifications class, whose content

feeds into the development of each of the other document types. The connections between the different

classes, and the manner in which they build upon the content of others is depicted by the arrows.

Figure 3: Diagram illustrating the framework for the standardization of liquid MNP products

The proposed structure is intended to allow the development and cross referencing of many interlinked

standards with the least possible confusion or amendment. Each application standard can draw upon the

specific documents which are relevant to it. Additional measurement and application standards may be

developed as and when the need arises.

3.5.2.2 Defined standardization methods and relevant parameters

SOPs that have been developed in WP4 for all measurement techniques we used in NanoMag were

published in D5.2. The SOPs have been prepared on the basis of a template [40] where the relevant points

needed for a successfully preparation of a SOP are summarized. Furthermore, already existing

standardization work was also considered in the SOPs. Furthermore, the SOPs have been established

Page 24: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

24

according the metrological checklist [16] providing guideline for a development of a standard. The SOPs

have been used by the analysis partner for a standardized characterization of single- and multi-core MNPs.

The synthesis project partners in WP3 have also developed SOPs describing established and harmonized

synthesis routine to produce MNP reference systems. These reference systems cover single- and multi-

core MNPs that may be used to test and verify different harmonized characterization procedures. The

developed SOPs (analysis and synthesis) has only been used by NanoMag partners during the time of the

project but will be used outside the NanoMag consortium in the new started MagNaStand project (EMPIR

project coordinated by PTB).

We classified the relevant parameters according to parameters needed to identify the material, structural

and magnetic parameters and properties assessing the MNP performance in final application. Here, we

took up the NanoMag achievements and we considered also the outcome of our third survey where project

partners and stakeholders have been asked what are the most important MNP properties that could be

defined for an international standard. In order to transfer all our results to the ISO/TC 229

“Nanotechnology” and to the currently developing standard ISO 19807 [41] and ISO TC/229 N 1421 [42],

four NanoMag partners (SP, NPL, PTB, CSIC) sent technical experts to their national standardization

organizations, with the exception of CSIC, we entered also ISO/TC229 WG4 “Nanotechnologies- Material

description” as technical experts. There, we used the NanoMag knowledge for active participation in the

development of new standards, which was also acknowledged by the convenor of the committee.

Furthermore, within the NanoMag project, we gave recommendations of entire MNP analyses utilizing a

variety of characterization methods. Flow charts illustrate divergent approaches of a particle system

analysis focusing different requirements to the characterization output.

We made a proposal for a unified technical specification sheet that contains the relevant MNP parameters.

Another important finding of the NanoMag work is that the decision which MNP parameter are relevant in

application and thus are important for standardization, this decision strongly depends on the specific

application. There is not even one parameter that is always needed in the description of MNPs.

3.5.2.3 Standardization road map

Our report D5.3 (standardization road map) summarizes the standardization work within the NanoMag

project. After a short survey of the definitions and the relevant parameters of MNPs, we illustrated the

current market trends and application of MNPs. We further showed our standardization strategy (see

Figure 3) that has been developed in [7].

We highlight the status and the roadmaps of European standardization bodies (CEN/IEC) with respect to

the standardization of nanoobjects and for ISO/TC 229 “Nanotechnology”, where we in detail present the

current and future activities in working group (WG)1 “Terminology and Nomenclature”, WG2

“Metrology and Characterization”, WG3 “Health, Safety and Environment” and WG4 “Material

Specifications”.

According to Figure 3, the standardization of MNP definitions and terminology has the highest hierarchy

for standardization. We thus gave an overview of which existing standard documents already cover the

characteristics of MNPs and we gave a recommendation for a roadmap for MNP terminology

standardization.

For the most relevant MNPs parameters and relating characterization methods that have been identified

during our work and which were revealed by surveys, we summarized the available standards.

We further noticed that for none of the relevant MNP biomedical applications standard documents exist so

far and we thus recommended also a roadmap for MNP application standardization.

Impact on other Work Packages

We gave feedback to WP3 regarding the synthesis of MNP system with specific properties with the aim to

verify and harmonize analysis methods to be used for standardization.We were in strong collaboration

with WP4 concerning the preparation of SOPs and Round Robin tests. We supported the partners in WP3

and WP4 in case of metrological issues and we provided the basis for the preparation of uncertainty

Page 25: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

25

budgets in WP4. We have continuously informed all NanoMag partners about the current activities at ISO

to that they had the opportunity to contribute in the development of work items.

WP6: Application and benchmarking

Work undertaken

This work package concerned the application and benchmarking of nanoparticles produced within the

project in WP3 as well as commercially available nanoparticles with the goal of tailoring the particle

properties to achieve improved performance in the chosen applications. Three application oriented

techniques were selected for this investigation, where each technique had its own set of requirements:

(1) Magnetic particle rotation

(2) Brownian relaxation

(3) Magnetic particle imaging

Below, we report the main results and achievements separately for each of the techniques and list the

publications resulting from the work.

Scientific and Technical Results

3.6.2.1 Magnetic particle rotation

The work was divided in three tasks: First we demonstrated the feasibility of measuring the nano-

mechanical stiffness of single proteins with MMPs (Task 6.1). In the next phase (Task 6.2) we

investigated whether the nano-mechanical stiffness could be related to the change in shape also denoted as

the conformation of a protein, which determines its function. In this study, we focused on cardiac

troponin, a protein released into the bloodstream upon heart failure and therefore an important biomarker

for cardiovascular diseases. In the third phase (Task 6.3), we explored the possibility to probe the

interaction between functionalized MMPs during their approach to functionalized substrates, an important

requisite for creating sandwiched proteins in applications.

All experimental work was carried out using a home-built quadrupole electromagnet, which acts as a

magnetic torque tweezer in combination with a microscope in order to monitor the rotation of the MMPs.

In order to visualize the rotation of a single MMP with the microscope, we used fluorescent particle labels

to break the rotational symmetry. Within the project we used both commercial particles (Dynal M-270,

Thermo-Fisher) as well as particles synthesized in the NanoMag consortium by partner SP. The latter

turned out to have a broad size distribution and the biofunctionalization turned out to be significantly more

challenging than for the commercially available particles. As a result, we decided to continue using the

commercially available Dynal M-270 particles. These particles were analysed within the consortium using

standard techniques described in WP5 as well as non-standard techniques quantifying the torque described

in the deliverables 6.1 and 6.2.

An impressive result, which illustrates the achieved goals of both task 6.1 and 6.2 is shown in Figure 4.

The angular deformation of a cardiac troponin protein complex is shown as function of time in a rotating

magnetic field (Task 6.1). The three figures illustrate a reversible change in twisting amplitude that can be

related to the conformation of the troponin complex present in a flow cell when the local calcium

concentration is altered. These conformations correspond to different stages of heart muscle contraction

induced by the local calcium concentration (Task 6.2).

Page 26: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

26

Figure 4: Angle of magnetic microparticle attached to substrate through a single troponin protein

complex recorded for several cycles of rotating magnetic field. The rotation direction of the field is

changed after approx. 5 min. Upon addition of Ca2+ (t = 30 min), a stiffening is observed as a

reduction of the angle excursions. Upon a reduction of the Ca2+ concentration (t = 60 min) the curve

obtained at t =0 min is recovered showing the stiffening to be reversible.

In biosensor applications, MMPs are magnetically pulled towards a surface to form the sandwiches that

are described above. The interaction potential of functionalized MMPs with the antibody coated surfaces

determines to a large extent the type of bond that will be formed and thereby the sensor performance. In

task 6.3 we explored probing this interaction potential with rotating MMPs. We analysed both the

magnetic field-induced particle rotation and the thermally induced random Brownian motion of the

particle when it approaches the surface. We varied the distance between the particles and the surface by

using a magnetic field to pull the particles towards the surface as well as the dilution of the buffer which

influences the electrostatic repulsion between the particle and the surface.

The measurements successfully identify two regimes of interactions that can be described by the particle

surface distance. These regimes can be explained by the particle-surface interaction potential (DLVO

theory), which predicts two energy minima separated by an energy barrier.

Experimental parameters determine that particles are either within a few nanometers from the surface with

a bond type that can be identified by the particle rotation behaviour (the primary minimum) or further

away in a secondary minimum. In this secondary minimum MMPs rotate with a significant friction to the

surface identified by the increasing phase lag to the rotating magnetic field. Here, the particles do not form

a molecular bond indicated by the relatively large translational, Brownian, motion amplitudes.

These measurements prove that magnetic particle rotation can be used to probe the interaction between

a functionalized MMP and a surface, which can be applied to optimize biosensor performance. The results

obtained in this activity are documented in [43] and in the manuscripts [44], [45].

3.6.2.2 Brownian Relaxation

This activity utilizes nanosized particles with sizes in the range of 100 nm and below to detect and

investigate biomolecules in a sample based on changes in the hydrodynamic size of the particles. The

ability of a particle to rotate in response to a rotating or oscillating magnetic field (Brownian relaxation)

depends on its size – smaller particles can rotate faster and follow the oscillating magnetic field up to

higher frequencies than larger particles. Therefore, measurements of the ability of the particles to rotate as

function of the frequency of the magnetic field can be used to estimate the size of the particles with

attached molecules. Several ways to use such measurements for bio-detection have been investigated in

the project.

The technique employed in the project is a newly developed and promising optomagnetic (OM) technique

that measures the intensity of light transmitted through a suspension of nanoparticles in response to an

oscillating magnetic field applied either along or perpendicular to the light path (Figure 5, right). The

technique has been further developed in the NanoMag project and evaluated on all new synthesised MNP

systems in the project. The technique takes advantage of the experimental fact that many particle systems

are not spherical and have a remanent magnetic moment along their long axis. Therefore, an applied

Page 27: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

27

oscillating magnetic field produces a modulation of the intensity of transmitted light as the particles rotate

to align their magnetic moments along the magnetic field.

In the project we have developed several setups for optomagnetic measurements (Task 6.4): (1) a setup that combines centrifugal microfluidic disk with OM measurements [46] (Figure 5, left)

(2) a setup that allows for simultaneous real-time measurements at a controllable temperature in four chips [47]

(3) a setup that allows for easy change of wavelength of the light

The principle of the technique has been described in detail by Fock et al [48].

Figure 5: left: Experimental setup where

the readout is integrated with lab-on-a-

disk sample handling. [46] right:

Principle of optomagnetic measurements.

The synchronous modulation of the light

transmitted through the sample in

response to an oscillating magnetic field

is measured using a photodetector.

We have developed a new quantitative method to determine the magnetic moment and the hydrodynamic

size of particles using OM measurements [48]. The method was applied to all particle systems synthetized

in WP3 and on some commercially available particle systems to identify the particle systems with the best

performance and to gain knowledge on which of the parameters of the particle systems that are important

for the quality of measurements on the particle suspensions (Task 6.5). We have also developed a method,

which uses AC Susceptibility (ACS) and OM measurements vs. field and frequency to obtain directly the

number-weighted magnetic moment and hydrodynamic size distribution, as well as the correlation

between the distributions. The method utilizes the nonlinear response of the particle at high magnetic field

strengths [49].

When used for bio-sensing, the optomagnetic method is used to measure changes in the hydrodynamic

size distribution and/or changes in the extinction properties of the MNP dispersion upon binding of target

bio-molecules to the MNPs. This binding could be detected as either an increase of the size of the

individual nanoparticles or as a change of the signal due to clustering of the nanoparticles. Using

commercial available magnetic nanoparticles (mainly multicore particles from partner Micromod with

diameters of 80 nm or 100 nm) we have used this principle ourselves or in collaboration (Task 6.6) to

detect:

• Coils of DNA formed by a rolling circle amplification (RCA) reaction [46]

• Monomerized (chopped up) rolling circle amplified DNA [50]

• Products formed from synthetic Dengue DNA by loop-mediated isothermal amplification (LAMP) and

detected in real-time during the reaction [51]

• C-Reactive Protein (CRP) and comparing/benchmarking to a readout on the same samples using AC

susceptibility [52]

• NS1 protein dengue biomarker in serum [53]

• prostate- specific antigen (PSA) using shape anisotropy enhanced optomagnetic measurement [54]

• Thrombin [55]

• the pH dependence of DNA triplex nanoswitches [47]

From the vast amount of particle systems synthesized in WP3, a limited set of candidates for bio-detection

was identified, and one particle system (prepared by Micromod) was selected and optimized for bio-

detection (Task 6.6). We obtained six different batches of this particle system, and optimized the probe

Page 28: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

28

density and the buffer used in the experiment. We were able to obtain slightly better performance with this

system compared to our conventional commercially available magnetic nanoparticles (also from

Micromod). We learned that the transition from a system showing reproducible physical properties to one

that also has reproducible performance after surface functionalization and exposure to bioassay conditions

should not be underestimated and is at least as demanding as defining the optimum physical properties.

During this activity, we have investigated and developed a new optomagnetic technique for

characterization and bio-detection. The technique has been applied on the characterization of the

hydrodynamic size and magnetic moment on essentially all particle systems in the project and the

information obtained (when possible) has been compared to alternative determinations. A variety of setups

have been developed and applied for the detection of a range of biomolecules using a range of different

detection strategies (see references for more information). Most of these experiments were performed

using commercially available nanoparticles produced by one of the project partners (Micromod), which

were also subject to characterization in WP4. A particle system – also prepared by Micromod – that

showed promising properties in physical measurements was selected and functionalized. However, the

performance of this system when used for bio-detection, under the conditions tested, was found to be only

marginally better than that used previously.

3.6.2.3 Magnetic particle imaging

The new tomographic imaging modality magnetic particle imaging (MPI) is able to combine high spatial

and temporal resolution with excellent sensitivity, opening new opportunities in clinical applications. The

principle of MPI is based on the nonlinear magnetization curve of superparamagnetic iron oxide

nanoparticles and does not stress the patient with harmful radiation. An overview of current scanner

topologies and tracer materials can be found in Panagiotopoulus et al. [56]. With optimized scanner

topologies and advanced tracers, a spatial submillimeter resolution is possible. In 2015, Bringout et al.

[57] introduced the first concept for a rabbit sized field free line MPI scanner. Also in 2015, Graeser et al.

[58] introduced a magnet particle spectroscopy (MPS) device which is able to generate field free point and

field free line field sequences while applying different possible offset fields. The flexibility of this

measurement device allows the comparison of different particle responses of different field sequences

with the same setup. A sensitivity study by Bente et al. [59] verified the linearity of the reconstructed

signal of a permanent magnet field free line MPI scanner with respect to the particle concentration of

Resovist (Bayer Schering Pharma AG, Berlin, Germany), which is used as a gold standard in MPI, and

found a lower detection limit of 15 μg iron in magnetite. In 2017, Dieckhoff et al. [60] were able to

demonstrate an improved MPI visualization of the liver applying Resovist and an enhanced system

function approach and multiple patches reconstructions.

In task 6.7 of WP6, we investigated the suitability of particles that were synthesized, analyzed and

standardized in the NanoMag consortium. The resolution study was performed using a magnetic particle

scanning device (preclinical MPI scanner, Bruker BioSpin GmbH, Ettlingen Germany) and three MPS

devices [Biederer et al., J. Phys. D Appl. Phys., 42(20), 2009; Graeser et al., Phys. Med. Biol., 62(9),

2017; Chen et al., IWMPI, 2017] to compare the particles regarding their sensitivity and spatial resolution.

Over all, three commercial particles selected in WP1, 28 particles synthesized in WP3 by CSIC, nanoPET,

micromod, DTU, and SP, as well as nine particles reproduced by nanoPET and micromod regarding to the

acquired standard operating procedures of WP5 were available. For reconstruction model-based, hybrid-

based as well as measurement-based reconstruction techniques were used as introduced amongst others in

Schmidt et al. [61] and von Gladiss et al. (Phys. Med. Biol., 62(9), 2017). All measurement results were

compared to the results of Resovist,

Using the results of MPS measurements [62], [63], all the above particles were compared in terms of

signal strength in MPI both with and without the presence of magnetic offset fields. Twenty-five particles

(two commercial, 14 synthesized, eight reproduced) were selected for further investigation considering

their performance.

Page 29: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

29

The evaluation of the measurement results identified some particles with a possible suitability for use in

MPI. The spatial resolution as well as the sensitivity of the particles showed results comparable to those of

Resovist. Figure 6 shows the reconstructed images of four particles with an emulated distance of 4 mT/µ0

corresponding to a spatial distance of 3.2 mm in the Bruker preclinical MPI scanner, including Resovist as

reference, FeraSpin R and MM08 as positive examples and CSIC07 as a negative example.

Figure 6: Reconstructed images of Resovist, FeraSpinR, MM08 and CSIC07 measured at 12 mT in x-

and y-directions with a sample volume of 10 µl and with an emulated distance of 4 mT/µ0

corresponding to a spatial distance of 3.2 mm in the Bruker preclinical MPI scanner.

In order to match some of the chemical and structural parameters of the particles with a possible MPI

suitability, parameters, such as the iron content, the particle shape and the core size as defined in the

technical data sheets or characterized by consortium members, were investigated. The comparison of those

parameters does not allow for the definition of a sharp quality criterion for the analysis and the synthesis

in respect to MPI devices. Neither the different synthesis methods nor the different particle coatings used

for the synthesis of the particles within the consortium seem to have a noticeable impact on the MPI

suitability. It can be stated though that particles with an iron core below 30 nm and an irregular or flower-

shaped core seem to be more suitable for MPI than particles with a spherical or rhombohedral core and a

core size above 30 nm. The results of this activity will be documented in [64].

Impact on other Work Packages

The partners in WP6 were in strong collaboration with WP4 and have contributed in the standardization

activities in WP5.

WP7: Dissemination and exploitation The main results in WP7 (dissemination and exploitation) are listed under “Potential Impact and Main

Dissemination Activities” section.

Potential Impact and Main Dissemination Activities (WP7: Dissemination and

exploitation) In the NanoMag project we see the following main impacts during the project.

• Clear nomenclature for describing structure and magnetic properties of MNPs

and MNP ensembles

• Improvements in reproducibility of MNP synthesis. Over 50 new MNP systems synthesized in the

project.

Page 30: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

30

• Excellent surveys of many common measurement methods for MNPs and their pros and cons,

classification of these methods including also classification of different types of MNP systems

• Stakeholder committee group connected to the NanoMag project.

• For some measurement methods: SOPs, uncertainty budgets, metrological descriptions

• Improved modelling of MNP magnetic properties, especially: dynamic behavior

• Correlation analysis between MNP parameters determined by different analysis methods

• Over 80 new publications in international high impact journals and over 160 presentations and

seminars carried out by NanoMag partners

• E-learning modules (NPL-web site, linked from the NanoMag homepage)

• Substantial contribution to ongoing ISO MNP standards (ISO 19807 ” Nanotechnology — Liquid

suspension of magnetic nanoparticles — Characteristics and measurements', PG14

"Superparamagnetic beads for free cell DNA extraction)

• Analysis service in the future (information will be collected at NanoMag homepage and PTB data

server)

• Continuation with the MagnaStand EU project coordinated by Uwe Steinhoff (PTB).

• Round Robin measurements (same analysis methods but in different labs) using different types of

MNP systems

• Our industrial partners in the project have commercialized some of the most promising MNP

systems that was synthesized during the project

The dissemination after the NanoMag project ended are described in the NanoMag exploitation plan.

Main results from the exploitation plan are described in the following text: “Within NanoMag project we

have identified three main types of exploitable outcomes. These are areas where the work that is currently

being done within the project can be used to generate impact, either directly, through the creation of best

practice and standards, or indirectly, through the upskilling of researchers and industry in the use of

MNPs.”

1. Standardisation practices and procedures. As with any emerging field of research that is finding

applications in industry, there is a need to ensure that users are supplied with the correct

information and supporting guidelines detailing what they are dealing with and how it should be

used. This information is currently lacking in the field of MNPs and is a necessary part of building

confidence in new products, from both users and investors, as well as ensuring that these products

are used correctly, which is especially important in the many medical applications that exist.

2. Services/measurement services. As this project represents the formation of a measurement

community for MNPs, it is important to be clear about the expertise and potential services that

exist and can be offered to both industry and academia.

3. Teaching aids such as e-learning products, best practice guides, and reports on standard operation

procedures (SOPs) that will make results accessible to users. Aimed more at students and new

researchers moving into the field, the production of teaching and learning resources will help to

train the next generation of researchers and provide established researchers with the capabilities

and understanding to pursue further research into the use of MNPs in biomedical science.

These three outcomes are further described in the following pages.

Initiation of new standards

In 2015 ISO/TC229 WG4 “Nanotechnologies – Material specification” started independently of

NanoMag the development of a material specification for MNPs (ISO 19807). Immediately, NanoMag

reacted to this development by sending technical experts to the national standard developing organisations

(SDOs) in the UK, Spain, Sweden and Germany, which are all countries with considerable industrial

involvement in the MNP sector. This was necessary, because NaoMag was the dominant pre-normative

Page 31: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

31

activity focusing on MNPs in Europe. In addition, these SDOs have now documented plans to adopt

ISO 19807 as a national standard. Except Spain, the NanoMag partners delegated their technical experts

also to ISO/TC229 WG4, where they subsequently contributed to the development of ISO 19807.

Currently ISO 19807 is in draft form with completion anticipated by the end of 2018. NanoMag partners

PTB, NPL, RISE Acreo, MICROMOD, and UCL will continue to work on ISO 19807 within the follow-

up project MagNaStand. A specific task in MagNaStand is to secure the public results of NanoMag and

make it available for further MNP standardisation at ISO and CEN level.

In September 2016, ISO/TC229 WG4 started to prepare a Preliminary Work Item “Specification for

superparamagnetic beads composed of nanoparticles for circulating tumour DNA extraction”. This

proposal did not come from NanoMag members. It has now been accepted and ISO has started the

development of the next standard involving MNPs under active contribution and involvement of the

NanoMag members. This new standard will directly affect a number of European SMEs and larger

companies working in the field. One European company, Roche-Diagnostics, has published a market

turnover in 2014 of 2.6 bln € with their immunodiagnostics (including reagents and instruments), which

are based on the use of MNPs1.

The NanoMag project has brought immense input into the development of these new standards, which

has been recognized several times by the ISO TC229/WG4 working group. In addition, an agreement has

been reached with the respective European standardisation committee CEN/TC352 “Nanotechnologies”

that the committee will support the developments at ISO and that, after finalization, it will adopt the ISO

standards as European normative documents.

Participation in other relevant MNP projects

Five members of the NanoMag consortium (NPL, RISE Acreo, DTU, PTB, UCL) are also active in the

TD COST network 1402 “RADIOMAG: Multifunctional Nanoparticles for Magnetic Hyperthermia and

Indirect Radiation Therapy”. This research network with over 140 participants covers several aspects of a

new cancer therapy based on MNPs. One workpackage is specifically dedicated to the standardisation of

MNP characterisation, where the NanoMag partners are actively involved. Participation of NanoMag

partners in a ring comparison of MNP heating characteristics was of a great importance, where the

NanoMag consortium supported the data analysis and interpretation for a larger number of participants.

Another goal within this is the setup of calibration samples for magnetic hyperthermia. The RADIOMAG

network will continue running until late 2018, well after the end of NanoMag.

Follow-up projects of MNP analysis standardisation (MagNaStand)

Acknowledging the situation that NanoMag does not have the necessary funding for a continuous

support of standardisation and it does not last long enough to finalise an ISO standards development, it

was necessary to create a follow-up project achieving these goals. For this reason, some members of the

NanoMag consortium initiated a new co-normative EMPIR project on MNPs, that in contrast to

NanoMag, which is a pre-normative project. In June 2017, the new project MagNaStand went into

operation. Participating NanoMag partners are PTB as the coordinator, NPL, UCL, RISE Acreo and

Micromod.

From the beginning, a strong collaboration and transmission of the results between NanoMag and

MagNaStand projects was envisaged. Specifically, in the MagNaStand working plan, a Task 3.1 is defined

under the title;” Knowledge transfer from the pre-normative EU FP7 project NanoMag”. The aim of this

task is to gather the metrological knowledge gained in the FP7 project NanoMag (2013-2017) and make it

available for the international standardisation of MNPs. The information collected from NanoMag will be

used within MagNaStand in the development of magnetic measurement methods, in the preparation of

metrological checklists and in the development of new standards at a national and an international level.

1 https://echa.europa.eu/documents/10162/8e0b0272-73d1-4e9a-8616-97ad9ee813d9

Page 32: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

32

Measurement Services

One of the most direct ways for this project to generate impact is through ensuring that companies and

researchers are aware of the services and expertise that exist in MNP metrology. In order to grow this

awareness NanoMag is currently carrying out the following actions:

A reference sheet for methodological standards will be made free and publicly available and will be

able to be downloaded from the NanoMag website (that still will be available and updated after the

NanoMag project). This reference sheet will be designed for the customers that buy MNP systems to be

used in specific applications (such as bio-separation, hyperthermia, or bio-sensing). Each of the

application areas are interested in different specifications of the MNP systems, however knowledge of the

particle size and particle morphology (single- or multi-core), and how to treat each of these, is required for

each application. Additionally, specific magnetic saturation value and initial magnetic susceptibility are

two important parameters that customers find valuable. This sheet will be updated on the NanoMag site up

to two years after the end of the project. After this point, one suggestion would be that the synthesis

partners will keep the NanoMag specifications for their MNP systems at their own websites. This would

be preferable to leaving an out-of-date copy on the NanoMag website for later reference, however, it

would require continued coordination.

The development of new samples or reproducing of old formulations and their characterisation – at cost

– may be possible after the project’s completion. It is desirable to maintain communication between the 17

partners of the NanoMag consortium after the project. This will create a post-NanoMag community and

allow external companies to contact this community (through project coordinator Christer Johansson RISE

Acreo as primary contact), if they require guidance on synthesis, analysis and standardisation of MNP

systems. In this case the NanoMag partners might charge such companies individually for each specific

consultancy or action.

In order to facilitate this interaction between companies and the NanoMag community ‘Yellow Pages’

of NanoMag techniques and contacts is being generated and will be able to download this from the

NanoMag website. This will be a directory stating what services each partner is capable of, which can be

used be industry to find relevant points of contact and increase awareness of what the consortium as a

whole can deliver. One example is an operation of the Core Facility “Metrology of Ultra-Low Magnetic

Fields” at PTB since June 2017. PTB grants external scientists from universities, international metrology

institutes and companies access to its know-how and its equipment for the measurement of extremely

small magnetic fields, explicitly including the thorough characterization of magnetic nanoparticles.

This directory will be held on the NanoMag website. It would be efficient to have this stored with the

reference sheet and linked across partner sites after updates of the NanoMag site cease. This would need to

be well organised with defined leads and a main site to hold the curated document. This would then be

shared with organisers of conferences and meetings on MNP systems to ensure that attendees are aware of

the extent of the community that has been established to assist in the standardisation and assurance of

MNP characterisation. The NanoMag website and the NanoMag data at the PTB server will be active after

the NanoMag project has ended.

Teaching/Learning

We understand that the setting of standards and the provision of services alone will not produce impact

if the requisite understanding does not exist in both the research and industrial communities. In order to

grow this understanding, NanoMag is producing tools and guidance for education in MNPs.

The main thrust of this outcome is being pursued through production of a series of e-Learning modules

under the common title Magnetic Nanoparticles: Standardisation and Biomedical Applications. The

course comprises 4 modules, linked to the knowledge and skills generated by the NanoMag project, each

of which covers a number of lessons on different subject areas and which will be freely available

indefinitely. The content and structure of the course is summarised in the course map below.

Page 33: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

33

Learners can take the modules individually as a stand-alone learning resource, or can undertake all four

together as a full e-Learning course. Information on these modules, including links to the e-Learning

course, can be found on the NanoMag website (www.nanomag-project.eu) and will remain live after the

website curation ends, i.e. two years after the project completion. The modules themselves are held on the

NPL e-learning website and will be accessible indefinitely. Up to now 132 people have already enrolled to

the first 2 modules. The number is expected to increase significantly when all modules are launched after

the end of the project.

For information on more routine processes, the project is developing best practice guides for specific

MNP measurement/characterisation that will be easily contextualised to relate to product information.

This will be led by PTB.

Stakeholder Surveys, Stakeholder meeting and Dissemination Conference

In order to maximise the output from the stakeholder participation, surveys were carried out in four

main areas. The surveys were implemented online using SurveyMonkey. These questions were typically

formatted in a binary or point based manner with the option to leave additional comments. The surveys

were carried out over the course of 36 months and concentrated on four main areas:

• Initial assessment of stakeholder/consortium interests and views.

• Characterisation techniques of MNP’s.

• Standards and role of standards in MNP industry.

• Performance of MNP’s in applications

The objective of the first survey was to form an initial assessment of the stakeholder interests and gauge

the general views of the stakeholder/consortium. The second survey concerned specific areas of

characterisation techniques of MNPs. The third survey concerned specific areas of standardisation and the

role of standards in the MNP industry. The fourth, and final, NanoMag survey looked at applications of

Page 34: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

34

MNPs and whether available particles limit performance of these applications. It also included questions

on the importance of MNPs' characteristics (such as single or multiple magnetic cores, hydrodynamic size

and colloidal stability) to their purpose.

During the project, we have had two major meetings, in connection to the ordinary project meetings, with

the NanoMag stakeholder committee (PTB Berlin M18 and at SP Stockholm M36). During these

meetings, we have discussed the standardization parameters that are important in industry and how these

are applied for instance in MNP synthesis process and analysis. We have also discussed the project result

uptake and how the results can be further be used in the future.

The final dissemination conference (deliverable D7.8) took place at Waterfront Hotel in Göteborg,

Sweden on 25-26 September 2017. The presentations were chosen to show the most scientific impacts in

the project related to; I) synthesis, II) analysis and II) applications. In total 52 attended the conference. The

NanoMag stakeholder committee was represented by Barry Moskowitz and Joachim Schwender

(Ferrotec), Lluis Martinez (Sepmag), Filiz Ibraimi (Lifeassays), Grete Irene Modahl (Thermofisher), Jose

Maria Abad (Nano Immunotech) and Gunnar Schütz (Bayer). Also, external participants invited by

NanoMag partners attended the conference. We got a very good response from both the stakeholders and

the NanoMag partners that the conference was very much appreciated.

Group picture from the final dissemination conference in Göteborg, September 2017.

During the project, over 80 publications submitted to international journals and over 180 presentations at

international conferences and seminars disseminating the NanoMag results (listed in template A1 and A2)

Website and Contact The NanoMag homepage can be found at http://www.nanomag-project.eu/home.html.

Contact:

Christer Johansson, Professor

Senior Expert

RISE Research Institutes of Sweden

Division ICT – RISE Acreo AB

+46 72 723 33 21

Arvid Hedvalls Backe 4, 400 14 Göteborg, Sweden

[email protected]

Page 35: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

35

References

[1] H. Gavilán et al., "Colloidal Flower-shaped Iron Oxide Nanoparticles: Synthesis Strategies and Coatings,"

Particle and Particle Systems Characterization, accepted, 2017.

[2] H. Gavilán et al., "Formation mechanism of maghemite nanoflowers synthesized by polyol mediated process,"

Chemistry of Materials, submitted, 2017.

[3] Y. Luengo et al., "Counterion and solvent effects on the size of magnetite nanocrystals obtained by oxidative

precipitation," J. Mater. Chem. C, no. 4, pp. 9482-9488, 2016.

[4] H. Gavilán et al., "How shape and internal structure affect the magnetic properties of anisometric magnetite

nanoparticles," Acta Materialia, no. 125, pp. 416-424, 2017.

[5] F. Vita et al., "Tuning morphology and magnetism of magnetite nanoparticles by calix[8]arene-induced oriented

aggregation," CrystEngComm, no. 18, pp. 8591-8598, 2016.

[6] H. Gavilán et al., "Controlling the size and the shape of uniform magnetic iron oxide nanoparticles for biomedical

applications," Chapter 1 in Clinical Applications of Magnetic Nanoparticles ISBN: 978-1-138-05155-3 Edited by

Nguyen T. K. Thanh, CRC Press, 2017.

[7] J. Wells et al., "Standardisation of Magnetic Nanoparticles in Liquid Suspension," J. Phys. D: Appl. Phys., no. 50,

p. 383003, 2017.

[8] L. Gutierrez et al., "Synthesis methods to prepare single- and multi-core iron oxide nanoparticles for biomedical

applications," Dalton Trans., no. 44, pp. 2943-2952, 2015.

[9] S. Bogren et al., "Classification of Magnetic Nanoparticle Systems—Synthesis, Standardization and Analysis

Methods in the NanoMag Project," Int. J. Mol. Sci., no. 16, pp. 20308-20325, 2015.

[10] F. Ludwig et al., "Optimization of Magnetic Nanoparticles for Magnetic Particle Imaging," IEEE Trans. Magn.,

no. 48(11), pp. 3780-3783, 2012.

[11] D. Eberbeck et al., "Multicore Magnetic Nanoparticles for Magnetic Particle Imaging," IEEE, no. 49, pp. 269-

274, 2013.

[12] S. Dutz et al, "Ferrofluids of magnetic multicore nanoparticles for biomedical applications," J. Magn. Magn.

Mater., no. 321, pp. 1501-1504, 2009.

[13] P. Hugounenq et al., "Iron oxide monocrystalline nanoflowers for highly efficent magnetic hyperthermia," J.

Phys. Chem. C, no. 116, pp. 15702-15712, 2012.

[14] O. Posth et al., "Classification of analysis methods for characterization of magnetic nanoparticle properties,"

Proc. IMEKO XXI World Congress, pp. 1362-1367, 2015.

[15] P. Bender et al., "Distribution functions of magnetic nanoparticles determined by a numerical inversion method,"

New J. Phys.,, no. 19, p. 073012, 2017.

[16] "ISO/TS229-IEC/TC113/JWG2 Metrological check-list for the use in preparation and evaluation of ISO NWIPs

and ISO WDs, ISO/TC N 673," 2010.

[17] F. Ludwig et al., "Size analysis of single-core magnetic nanoparticles," J. Magn. Magn. Mater., no. 427, pp. 19-

24, 2017.

[18] F. Ludwig et al., "Dynamic Magnetic Properties of Optimized Magnetic Nanoparticles for Magnetic Particle

Imaging," IEEE Transactions on Magnetics, no. 50(11), pp. 1-4, 2014.

[19] F. Ludwig et al., IEEE Trans. Magn., in press, 2017.

[20] J. Dieckhoff et al., "Magnetic-field dependence of Brownian and Néel relaxation times," J. Appl. Phys., no. 119,

pp. 043903-1-8, 2016.

[21] E. Wetterskog et al., "Tuning the structure and habit of iron oxide mesocrystals," Nanoscale, no. 8, p. 15571,

2016.

[22] P. Bender et al., "Structural and magnetic correlations of multi-core nanoparticles revealed by a generalised

numerical inversion method," Sci. Rep., no. 7:45990, 2017.

[23] E. Wetterskog et al., "Size and property bimodality in magnetic nanoparticle dispersions: single domain particles

vs. strongly coupled nanoclusters," Nanoscale, no. 9, pp. 4227-4235, 2017.

[24] T. Yoshida et al., "Effect of alignment of easy axes on dynamic magnetization of immobilized magnetic

nanoparticles," J. Magn. Magn. Mater., no. 427, pp. 162-167, 2017.

[25] N. Löwa et al., "Magnetic nanoparticles in different biological environments analyzed by magnetic particle

spectroscopy," J. Magn Magn. Mater., no. 427, pp. 133-138, 2017.

[26] T. Viereck et al., "Dual-frequency magnetic particle imaging of the Brownian particle contribution," J. Magn.

Page 36: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

36

Magn. Mater., no. 427, pp. 156-161, 2017.

[27] D. Heinke et al., "Diffusion-Controlled Synthesis of Magnetic Nanoparticles," International Journal on Magnetic

Particle Imaging, no. 2(1), pp. 1603001-1-4, 2016.

[28] K. Witte et al., "Particle size- and concentration-dependent separation of magnetic nanoparticles," J. Magn.

Magn. Mater., no. 427, pp. 320-324, 2017.

[29] J. Sommertune et al., "Polymer/Iron Oxide Nanoparticle Composites—A Straight Forward and Scalable Synthesis

Approach," Int. J. Mol. Sci., no. 16, pp. 19752-19768, 2015.

[30] D. F. Coral et al., "Effect of Nanoclustering and Dipolar Interactions in Heat Generation for Magnetic

Hyperthermia," Langmuir, no. 32 (5), pp. 1201-1213, 2016.

[31] K. Simeonidis et al., "In-situ particles reorientation during magnetic hyperthermia application: Shape matters

twice," Sci. Rep., no. 6, p. 38382, 2016.

[32] W. Szczerba et al., "SAXS analysis of single- and multi-core iron oxide magnetic nanoparticles," J. Appl. Cryst.,

no. 50, pp. 481-488, 2017.

[33] A. Lak et al., "Resolving particle size modality in bi-modal iron oxide nanoparticle suspension," J. Magn. Magn.

Mater., no. 380, pp. 140-143, 2015.

[34] A. Joos et al., "Size-dependent MR relaxivities of magnetic nanoparticles," J. Magn. Magn. Mater., no. 427, pp.

122-126, 2017.

[35] D. Schmidt et al., "Finding the magnetic size distribution of magnetic nanoparticles from magnetization

measurements via the iterative Kaczmarz algorithm," J. Magn Magn. Mater., no. 431, pp. 33-37, 2017.

[36] J. Leliaert et al., "Interpreting the magnetorelaxometry signal of suspended magnetic nanoparticles with

Kaczmarz' algorithm," J. Phys. D: Appl. Phys., no. 50, p. 195002, 2017.

[37] J. Leliaert et al., "The complementarity and similarity of magnetorelaxometry and thermal magnetic noise

spectroscopy for magnetic nanoparticle characterization," J. Phys. D: Appl. Phys., no. 50, p. 085004, 2017.

[38] S. Draack et al., "Temperature-dependent MPS measurements," International Journal on Magnetic Particle

Imaging, p. 3(1), 2017.

[39] J. Fock and L. K. Bogart et al., "Uncertainty budget for determinations of mean isomer shift from Mössbauer

spectra," Hyperfine Interact., no. 237(1), pp. 1-11, 2016.

[40] http://www.nanopartikel.info/en/nanoinfo/methods/992-operating-instructions.

[41] "ISO 19807 Nanotechnology -- Liquid suspension of magnetic nanoparticles -- Characteristics and

measurements".

[42] "ISO N 1421 Nanotechnologies – Specification for superparamagnetic beads composed of nanoparticles for

circulating tumor DNA extraction".

[43] F. A. Gutierrez Mejia, "Proteins with a Twist: Torsion Profiling of Proteins at the Single Molecule, PhD Thesis,

Technical University of Eindhoven," 2016.

[44] C. M. Moerland et al., "Rotating Magnetic Beads for Lab-on-a-Chip Biosensing – A Comprehensive Review,"

Lab Chip, invited review - in preparation, 2017.

[45] F. A. Gutierrez Mejia et al., "Single Protein Conformation Switching Revealed by Antibody Targeting and

Torque," in preparation, 2017.

[46] M. Donolato et al., "Quantification of Rolling Circle Amplified DNA Using Magnetic Nanobeads and a Blu-Ray

Optical Pick-up Unit," Biosens. Bioelectron., no. 67, pp. 649-655, 2015.

[47] G. A. S. Minero et al., "Optomagnetic Detection of DNA Triplex Nanoswitches," Analyst, no. 142(4), pp. 582-

585, 2017.

[48] J. Fock et al., "Characterization of fine particles using optomagnetic measurements," Phys. Chem. Chem. Phys.,

no. 19, p. 8802, 2017.

[49] J. Fock et al., "Field-Dependent Dynamic Magnetic and Optical Responses from Magnetic Nanoparticle

Ensembles Displaying Brownian Relaxation," in preparation, 2017.

[50] A. Mezger et al., "Scalable DNA-Based Magnetic Nanoparticle Agglutination Assay for Bacterial Detection in

Patient Samples," ACS Nano, no. 9(7), pp. 7374-7382, 2015.

[51] G. A. S. Minero et al., "Sequence-Specific Validation of LAMP Amplicons in Real-Time Optomagnetic

Detection of Dengue Serotype 2 Synthetic DNA," Analyst, 2017.

[52] J. Fock et al., "Comparison of Optomagnetic and AC Susceptibility Readouts in a Magnetic Nanoparticle

Agglutination Assay for Detection of C-Reactive Protein," Biosens. Bioelectron., 2016.

[53] P. Antunes et al., "Quantification of NS1 Dengue Biomarker in Serum via Optomagnetic Nanocluster Detection,"

Page 37: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

37

Sci. Rep., no. 5, p. 16145, 2015.

[54] B. Tian et al., "Shape Anisotropy Enhanced Optomagnetic Measurement for Prostate-Specific Antigen Detection

via Magnetic Chain Formation," Biosens. Bioelectron., no. 98, pp. 285-291, 2017.

[55] R. Uddin et al., "Lab-on-a-Disc Agglutination Assay for Protein Detection by Optomagnetic Readout and Optical

Imaging Using Nano- and Micro-Sized Magnetic Beads," Biosens. Bioelectron., no. 85, pp. 351-357, 2016.

[56] N. Panagiotopoulos et al., " Magnetic particle imaging: current developments and future directions," International

Journal of Nanomedicine, no. 10, p. 3097, 2015.

[57] G. Bringout et al., "Concept of a rabbit-sized FFL-scanner," International Workshop for Magnetic Particle

Imaging, p. 49, 2015.

[58] M. Graeser et al., "A Device for Measuring the Trajectory Dependent Magnetic Particle Performance for MPI,"

International Workshop for Magnetic Particle Imaging, p. 96, 2015.

[59] K. Bente et al., "Sensitivity study for an MPI FFL scanner," International Workshop on Magnetic Particle

Imaging, p. 88, 2015.

[60] J. Dieckhoff et al., “In vivo liver visualizations with magnetic particle imaging based on the calibration

measurement approach,” Physics in Medicine and Biology, no. 62(9), p. 3470, 2017.

[61] D. Schmidt et al., "Imaging characterization of MPI tracers employing offset measurements in a two

dimensional magnetic particle spectrometer," International Journal on Magnetic Particle Imaging, p. 2, 2016.

[62] C. Debbeler et al., "MPS study on new MPI tracer material," International workshop on Magnetic Particle

Imaging, p. 113, 2016.

[63] C. Debbeler et al., "Investigation on new MPI tracer material," International Workshop on Magnetic Particle

Imaging, p. 71, 2017.

[64] C. Debbeler et al., “Resolution study on new MPI tracer material,” International Workshop on Magnetic Particle

Imaging, in preparation 2018.

Page 38: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

38

4.2 Use and dissemination of foreground

Page 39: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

39

Section A (public)

▪ Table A1: List of all scientific (peer reviewed) publications relating to the foreground of the project.

▪ Table A2: List of all dissemination activities (publications, conferences, workshops, web sites/applications, press releases, flyers, articles

published in the popular press, videos, media briefings, presentations, exhibitions, thesis, interviews, films, TV clips, posters).

TABLE A1: LIST OF SCIENTIFIC (PEER REVIEWED) PUBLICATIONS, STARTING WITH THE MOST IMPORTANT ONES

NO.

Title Main

author

Title of the periodical

or the series

Number, date or

frequency,Volume

Publisher Place of

publication

Year of publicatio

n

Relevant pages

Permanent identifiers2 (if available)

Is/Will open access3 provided to this

publication?

1 Counterion and solvent effects on the size of magnetite nanocrystals obtained by oxidative precipitation

Y. Luengo

Journal of Materials Chemistry C

Vol. 4, No. 40 RSC CAMBRIDG

E CB4 0WF,

CAMBS,

ENGLAND

2016 9482-9488

DOI: 10.1039/C6TC03567A

2 Tuning Morphology and Magnetism of Magnetite Nanoparticles by Calix[8]arene-Induced Oriented Aggregation

F. Vita CrystEngComm

18

RSC UK 2016

8591-8598

DOI: 10.1039/x0xx00000x

3 Studies of the Colloidal Properties of Superparamagnetic Iron

G. B. da Silva

J. Braz. Chem. Soc.

28

Sociedad Brasileira de

Brazil 2017

731-739

DOI: http://dx.doi.org/10.21577/0103-5053.20160221

2 A permanent identifier should be a persistent link to the published version full text if open access or abstract if article is pay per view) or to the final manuscript accepted for publication (link to

article in repository). 3 Open Access is defined as free of charge access for anyone via Internet. Please answer "yes" if the open access to the publication is already established and also if the embargo period for open

access is not yet over but you intend to establish open access afterwards.

Page 40: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

40

Oxide Nanoparticles Functionalized with Platinum Complexes in Aqueous and PBS Buffer Media

Quimica

4 Superlattice growth and rearrangement during evaporation-induced nanoparticle self-assembly

E. Josten Scientific Reports

7

Nature Publishing Group

UK 2017

2802

DOI: 10.1038/s41598-017-02121-4

yes

5 Characterization of fine particles using optomagnetic measurements

J. Fock Phys. Chem. Chem. Phys.

19

RSC UK 2017

8802-8814

DOI: http://dx.doi.org/10.1039 /C6CP08749C

6 Controlling the size and the shape of uniform magnetic iron oxide nanoparticles for biomedical applications.

H. Gavilán

Clinical Applications of magnetic Nanoparticles

CRC Press/Tylor & Francis

USA/UK To be published

ISBN: 978-1-138-05155-3.

7 Analysis of ac susceptibility spectra for the characterization of magnetic nanoparticles

F. Ludwig

IEEE Trans. Magn.

PP,99

IEEE Magnetics Society

USA 2017

1

DOI: 10.1109/TMAG.2017.2693420

8 Structural and magnetic properties of multi-core nanoparticles analysed using a generalised numerical inversion method

P. Bender

Scientific Reports

7

Nature Publishing Group

UK 2017

45990

DOI: 10.1038/srep45990 yes

9 Commentary on the clinical and preclinical dosage limits of interstitially administered magnetic fluids for therapeutic hyperthermia based on current practice and efficacy models

P. Southern

International Journal of Hyperthermia

Informa Healthcare

UK

Page 41: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

41

10 The anisotropy of the ac susceptibility of immobilized magnetic nanoparticles – the influence of intra-potential-well contribution on the ac susceptibility spectrum

F. Ludwig

IEEE Trans. Magn.

PP,99

IEEE Magnetics Society

USA 2017

1-1

DOI: 10.1109/TMAG.2017.2692038

11 On the interpretation of Mössbauer spectra of magnetic nanoparticles

J. Fock JMMM

445

Elsevier NL 2017

11-21

DOI: https://doi.org/10.1016/j.jmmm.2017.08.070

12 Formation mechanism of maghemite nanoflowers synthesized by polyol mediated process

H. Gavilán

ACS Omega

ACS USA 2017

Accepted

13 Sequence-specific validation of DNA amplicons in LAMP for real-time detection of Dengue virus DNA using magnetic nanoparticles

G.A.S. Minero

Analyst

142

RSC UK 2017

3441-3450

DOI: dx.doi.org/10.1039/C7AN01023K.

14 Unraveling viscosity effects on the hysteresis losses of magnetic nanocubes

D. Cabrera

Nanoscale

9

RSC UK 2017

5094-5101

DOI: 10.1039/C7NR00810D

15 Nanopartículas en biomedicina (in Spanish)

E. Esteban

Biotech Magazine 24

Biotech Spain 2014

yes

16 Precise control over shape and size of iron oxide nanocrystals suitable for assembly into ordered particle arrays

E. Wetterskog

Science and Technology of Advanced Materials

15

Taylor & Francis

UK 2014

55010

DOI: https://doi.org/10.1088/1468-6996/15/5/055010

yes

17

Lab-on-Blu-ray: Low-cost analyte detection on a disk

M. Donolato

Proc. 18th Int. Conf. on Miniaturized Systems for

2014

2044-2046

Page 42: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

42

Chemistry and Life Sciences (MicroTAS 2014), San Antonio, Texas, USA, pp. 2044-2046 (2014).

18 Practical Applications of Asymmetrical Flow Field-Flow Fractionation (AF4): A Review

M. Leeman

LCGC Europe, Volume 28,

Issue 12

2015

642–651

19 Effective Particle Magnetic Moment of Multi-Core Particles

F. Ahrentorp

JMMM

380

Elsevier NL 2015

221-226

DOI:10.1016/j.jmmm.2014.09.070

20 Resolving particle size modality in bi-modal iron oxide nanoparticle suspensions

A. Lak JMMM

380

Elsevier NL 2015

140-143

DOI:10.1016/j.jmmm.2014.08.050

21 Synthesis Methods to Prepare Single- and Multi-core Magnetic Nanoparticles for Biomedical Applications

L. Gutiérrez

Dalton Trans.

44

RSC UK 2015

2943-2952

DOI: 10.1039/c4dt03013c

22 Magnetic nanoparticle detection using domain wall-based nanosensor

H. Corte-Léon

J. Appl. Phys.

117

AIP USA 2015

17E313

DOI: http://dx.doi.org/10.1063/1.4914365

23 Improving magnetic properties of ultrasmall magnetic nanoparticles by biocompatible coatings

R. Costo J. Appl. Phys.

117

AIP USA 2015

64311

DOI: http://dx.doi.org/10.1063/1.4908132

24 Degradation of magnetic nanoparticles mimicking lysosomal conditions followed by ac

L. Gutiérrez

Biomedical Engineering/Biomedizinische 60(5)

D 2015

417-425

DOI: 10.1515/bmt-2015-0043

Page 43: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

43

susceptibility Technik

25 Scalable DNA-based magnetic nanoparticle agglutination assay for bacterial detection in patient samples

A. Mezger

ACS Nano

9

ACS USA 2017

7374-7382

DOI: 10.1021/acsnano.5b02379

26 Blu-ray based optomagnetic aptasensor for detection of small molecules

J. Yang Biosens. Bioelectron.

75

Elsevier

NL 2016

396-403

DOI:10.1016/j.bios.2015.08.062

27 Polymer/Iron Oxide Nanoparticle Composites—A Straight Forward and Scalable Synthesis Approach

J. Sommertune

International Journal of Molecular Science

16

MDPI CH 2015

19752-19768

DOI:10.3390/ijms160819752

28 Classification of Magnetic Nanoparticle Systems—Synthesis, Standardization and Analysis Methods in the NanoMag Project

S. Bogren

International Journal of Molecular Science

16

MDPI CH 2015

20308-20325

DOI: 10.3390/ijms160920308.

29 Magnetic scanning gate microscopy of a domain wall nanosensor using microparticle probe

H. Corte-Léon

JMMM

400

Elsevier NL 2016

225-229

DOI:10.1016/j.jmmm.2015.07.116

30 Quantification of NS1 dengue biomarker in serum via optomagnetic nanocluster detection

P. Antunes

Scientific Reports

5

Nature Publishing Group

UK 2015

16145

DOI: 10.1038/srep16145

yes

31 Thermal magnetic noise spectra of nanoparticle ensembles

J. Leliaert

Appl. Phys. Lett.

107

AIP USA 2015

222401

DOI:10.1063/1.4936890

32 Turn-on optomagnetic bacterial DNA sequence detection using volume-amplified magnetic nanobeads

R.S. Bejhed

Biosens. Bioelectron.

66

Elsevier NL 405-411

DOI: 10.1016/j.bios.2014.11.048

33 Optomagnetic read-out R.S. Biotechnolo 10 Wiley- USA 2015 469-472 DOI: 10.1002/biot.201400615

Page 44: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

44

enables easy, rapid, and cost-efficient qualitative biplex detection of DNA sequencies

Bejhed gy Journal Blackwell

34 Magnetophoretic transport line system for rapid on-chip attomole protein detection

R.S. Bejhed

Langmuir

31

ACS USA 2015

10296-10302

DOI: 10.1021/acs.langmuir.5b01947

35 Magnetic nanobeads present during enzymatic amplification and labeling for a simplified DNA detection protocol based on AC susceptometry

R.S. Bejhed

AIP Advances

5

AIP USA 2015

127139

DOI: http://dx.doi.org/10.1063 /1.4939570

yes

36

Classification of analysis methods for characterization of magnetic nanoparticle properties

O. Posth Proc. XXI IMEKO World Congress “Measurement in Research and Industry”, Prague, Czech Republic

2015

1362-1367

37 Uncertainty budget for determinations of mean isomer shift from Mössbauer spectra

J. Fock Hyperfine Interactions

237

Springer D? 2016

23

DOI:10.1007/s10751-016-1253-1

38 Detection of a magnetic bead by hybrid nanodevices using scanning gate microscopy

H. Corte-Léon

AIP Advances

6

AIP USA 2016

56502

DOI: 10.1063/1.4943147

yes

39 Magnetic particle J. Wells IEEE Trans. IEEE DOI:

Page 45: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

45

nanosensors implementing nucleation events in perpendicular anisotropy materials

Magn. Magnetics Society

10.1109/TMAG.2016.2524074,

40

SOL-GEL MAGNETIC MATERIALS

L. Gutiérrez

In The Sol-Gel Handbook. Synthesis, Characterization, and Applications

WILEY-VCH,

2015

813-840

ISBN: 9783527334865

41 Interacting Superparamagnetic Iron(II) Oxide Nanoparticles: Synthesis and Characterization in Ionic Liquids

B.C. Leal Inorg. Chem.

55

ACS USA 2016

865-870

DOI: 10.1021/acs.inorgchem.5b02320

42 Effect of Nanoclustering and Dipolar Interactions in Heat Generation for Magnetic Hyperthermia

D. Coral Langmuir

32

ACS USA 2016

1201-1213

DOI: 10.1021/acs.langmuir.5b03559

43 Magnetic-field dependence of Brownian and Neel relaxation times

J. Dieckhoff

J. Appl. Phys.

119

AIP USA 2016

43903

DOI: 10.1063/1.4940724

44

Diffusion-Controlled Synthesis of Magnetic Nanoparticles

D. Heinke

International Journal of Magnetic Particle Imaging 2

ISP D 2016

1

DOI: 10.18416/ijmpi.2016.1603001

45 Imaging Characterization of MPI Tracers Employing Offset Measurements in a two Dimensional Magnetic Particle Spectrometer

D. Schmidt

International Journal of Magnetic Particle Imaging

2

ISP D 2016

1

DOI: 10.18416/ijmpi.2016.1604002

46 Magnetic readout of M.F. Chapter in Springer DOI: http://dx.doi.org/10.1007

Page 46: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

46

rolling circle amplification products

Hansen “Rolling Circle Amplification (RCA): Toward New Clinical Diagnostics and Therapeutics”

International Publishing,

/978-3-319-42226-8

47 Lab-on-a-disc agglutination assay for protein detection by optomagnetic readout and optical imaging using nano- and micro-sized magnetic beads

R. Uddin Biosens. Bioelectron.

85

Elsevier NL 2016

351-357

DOI: http://dx.doi.org/10.1016 /j.bios.2016.05.023

48 In-situ particles reorientation during magnetic hyperthermia application: Shape matters twice

K. Simeonidis

Scientific Reports

6

Nature Publishing Group

UK 2016

38382

DOI: 10.1038/srep38382

yes

49 Finding the magnetic size distribution of magnetic nanoparticles from magnetization measurements via the iterative kaczmarz algorithm

D. Schmidt

JMMM

431

Elsevier NL 2017

33-37

DOI: 10.1016/j.jmmm.2016.09.108

50 Size analysis of single-core magnetic nanoparticles

F. Ludwig

JMMM

427

Elsevier NL 2017

19-24

DOI: 10.1016/j.jmmm.2016.11.113

51 Tuning the structure and habit of iron oxide mesocrystals

E. Wetterskog

Nanoscale

8

RSC UK 2016 15571-15580

DOI: 10.1039/c6nr03776c

52 Magnet-bead based microRNA delivery

P. Müller Stem Cells Internationa 2016

Hindawi Egypt 2016 7152761

DOI: http://dx.doi.org/10.1155/2016/

yes

Page 47: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

47

system to modify CD133 + stem cells

l 7152761

53 Multi-scale magnetic nanoparticle based optomagnetic bioassay for sensitive DNA and bacteria detection

B. Tian Anal. Methods

2016

RSC UK 2016

5009-5016

DOI: dx.doi.org/10.1039/c6ay00721j

54 Blue-ray optomagnetic measurement based competitive immunoassay for Salmonella detection

B. Tian Biosens. Bioelectron.

77

Elsevier NL 2016

32-39

DOI: 10.1016/j.bios.2015.08.070

55 Size and property bimodality in magnetic nanoparticle dispersions: single domain particles vs. strongly coupled nanoclusters

E. Wetterskog

Nanoscale

9

RSC UK 2017

4227-4235

DOI: 10.1039/c7nr00023e

56 Colloidal Flower-shaped Iron Oxide Nanoparticles: Synthesis Strategies and Coatings

H. Gavilán

Particle & Particle Systems Characterization 34

Wiley USA 2017

1700094

DOI: 10.1002/ppsc.201700094

57 How shape and internal structure affect the magnetic properties of anisometric magnetite nanoparticles

H. Gavilán

Acta Materialia

125

Elsevier NL 2017

416-424

DOI: 10.1016/j.actamat.2016.12.016

58 Interpreting static and dynamic magnetization behavior of magnetic nanoparticles in terms of magnetic moment and energies

U. Steinhoff

JMMM

Elsevier NL 2016

DOI: 10.1016/j.jmmm.2016.11.021

59 Magnetic Nanoparticles in Different Biological Environments analyzed by Magnetic Particle

N. Löwa JMMM

427

Elsevier NL 2017

133-138

DOI: https://doi.org/10.1016/j.jmmm.2016.10.096

Page 48: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

48

Spectroscopy

60 Comparison of optomagnetic and AC susceptibility readouts in a magnetic nanoparticle agglutination assay for detection of C-reactive protein

J. Fock Biosens. Bioelectron.

88

Elsevier NL 2017

94-100

DOI: https://doi.org/10.1016/j.bios.2016.07.088

61 Exchange-biased AMR bridges for magnetic field sensing and biosensing

M.F. Hansen

IEEE Trans. Magn.

53

IEEE Magnetics Society

USA 2016

4000211

DOI: 10.1109/TMAG.2016.2614012

62 Optomagnetic detection of DNA triplex nanoswitches

G.A.S. Minero

Analyst

142

RSC UK 2017

582-585

DOI: 10.1039/c6an02419j

63 Dual-frequency magnetic particle imaging of the Brownian particle contribution

T. Viereck

JMMM

427

Elsevier NL 2016

156-161

DOI: https://doi.org/10.1016/j.jmmm.2016.11.003

64 Size analysis of single-core magnetic nanoparticles

F. Ludwig

JMMM

427

Elsevier NL 2016

19-24

DOI: https://doi.org/10.1016/j.jmmm.2016.11.113

65 Effect of alignment of easy axes on dynamic magnetization of immobilized magnetic nanoparticles

T. Yoshida

JMMM

427

Elsevier NL 2016

162-167

DOI: https://doi.org/10.1016/j.jmmm.2016.10.040

66 The Complementarity and Similarity of Magnetorelaxometry and Thermal Magnetic Noise Spectra for Magnetic Nanoparticle Characterization

J. Leliaert

J. Phys. D: Appl. Phys.

50

IOP UK 2017

85004

DOI: 10.1088/1361-6463/aa5944

67 Interpreting the magnetorelaxometry signal of suspended magnetic nanoparticles

J. Leliaert

J. Phys. D: Appl. Phys.

50

IOP UK 2017

195002

DOI: 10.1088/1361-6463/aa695d

Page 49: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

49

with Kaczmarz’ algorithm

68 Combined anomalous Nernst effect and thermography studies of ultrathin CoFeB/Pt nanowires

J. Wells AIP Advances

7

AIP USA 2016

55904

DOI: dx.doi.org/10.1063/1.4973196

yes

69 Switchable bi-stable multilayer magnetic probes for imaging of soft magnetic structures

T. Wren Ultramicroscopy

179

Elsevier NL 2017

41-46

DOI: dx.doi.org/10.1016/j.ultramic.2017.03.032

70 V-shaped domain wall probes for calibrated magnetic force microscopy'

R. Puttock

IEEE Trans. Magn.

PP,99

IEEE Magnetics Society

USA 2017

1-1

DOI: 10.1109/TMAG.2017.2694324

71 Detection of individual iron-oxide nanoparticles with vertical and lateral sensitivity using domain wall nucleation in CoFeB/Pt nanodevices

J. Wells AIP Advances

7

AIP USA 2017

56715

DOI: http://dx.doi.org/10.1063/1.4975357

yes

72 Magnetic scanning gate microscopy of CoFeB lateral spin valve

H. Corte-Léon

AIP Advances

7

AIP USA 2017

56808

DOI: dx.doi.org/10.1063/1.4977891

yes

73 Size and property bimodality in magnetic nanoparticle dispersions: single domain particles vs. strongly coupled nanoclusters

E. Wetterskog

Nanoscale

9

RSC UK 2017

4227-4235

DOI: 10.1039/C7NR00023E

74 Hybrid normal metal/ferromagnetic nanojunctions for domain wall tracking

H. Corte-Léon

Scientific Reports

7

Nature Publishing Group

UK 2017

6295

DOI: 10.1038/s41598-017-06292-y

yes

75 Calibration of multilayered magnetic force microscopy probes

V. Panchal

Scientific Reports

7

Nature Publishing Group

UK 2017

7224

DOI: 10.1038/s41598-017-07327-0

yes

76 Angular Magnetoresistance of

H. Moham

IEEE Trans. Magn. PP,99

IEEE Magnetics

USA 2017 1-1

DOI: 10.1109/TMAG.2017.2718623

Page 50: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

50

Nanowires with Alternating Cobalt and Nickel Segments

mad Society

77 Nanoscale thermoelectrical detection of magnetic domain wall propagation

P. Krzysteczko

Phys. Rev. B

95

APS USA 2017

220410(R)

DOI: https://doi.org/10.1103/PhysRevB.95.220410

78 On the ‘centre of gravity’ method for measuring the composition of magnetite/maghemite mixtures, or the stoichiometry of magnetite-maghemite solid solutions, via 57Fe Mössbauer spectroscopy

J. Fock J. Phys. D: Appl. Phys.

50

IOP UK 2017

265005

DOI: https://doi.org/10.1088/1361-6463/aa73fa

79 Shape anisotropy enhanced optomagnetic measurement for prostatespecific antigen detection via magnetic chain formation

B. Tian Biosens. Bioelectron.

98

Elsevier UK 2017

285-291

DOI: https://doi.org/10.1016/j.bios.2017.06.062

80 Distribution functions of magnetic nanoparticles determined by a numerical inversion method

P. Bender

New Journal of Physics

19

IOP UK 2017

73012

DOI: https://doi.org/10.1088/1367-2630/aa73b4

yes

81 Standardisation of Magnetic Nanoparticles in Liquid Suspension

J. Wells J. Phys. D: Appl. Phys.

50

IOP UK 2017

383003

DOI: http://iopscience.iop.org/article/10.1088/1361-6463/aa7fa5

82 Size-dependent MR relaxivities of magnetic nanoparticles

A. Joos JMMM

427

Elsevier NL 2017

122-126

DOI: https://doi.org/10.1016/j.jmmm.2016.11.021

Page 51: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

51

TABLE A2: LIST OF DISSEMINATION ACTIVITIES

NO. Type of activities4 Main leader Title Date Place Type of

audience5

Size of audience

Countries addressed

1 Conference European Conference on

Nanotechnologies 26 February 2010

2 International Workshop on Magnetic Particle Imaging

(Poster)

K. Lüdtke-Buzug (UZL)

Viscosity Affected Determination of Iron Concentration of MPI

Tracers Based on µCT

March 2014 Berlin, Germany Scientific 200 International

3 4th Zing Bionanomaterials

conference (Invited)

Quentin Pankhurst

(UCL)

Translational R&D in Healthcare

Biomagnetics April 2014 Nerja, Spain Scientific -- International

4 Intermag Conference

(Oral) ALL

Magnetic, structural and particle size analysis of single- and multi-core

magnetic nanoparticles in the NanoMag project

May 2014 Dresden, Germany Scientific -- International

5 Magnetic carrier Conference

(Poster) C. Jonasson

(Acreo)

Effective Particle Magnetic Moment of Multicore Particles

June 2014 Dresden, Germany Scientific -- International

6 Magnetic carrier Conference

(Poster) K. Lüdtke-

Buzug (UZL)

Micro-CT based Determination of

Ferrofluid Iron Concentration

June 2014 Dresden, Germany Scientific -- International

4 A drop down list allows choosing the dissemination activity: publications, conferences, workshops, web, press releases, flyers, articles published in the popular press, videos, media

briefings, presentations, exhibitions, thesis, interviews, films, TV clips, posters, Other. 5 A drop down list allows choosing the type of public: Scientific Community (higher education, Research), Industry, Civil Society, Policy makers, Medias ('multiple choices' is possible.

Page 52: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

52

7 Magnetic carrier Conference

(Oral)

Christer Johansson

(Acreo) EU FP7: NanoMag June 2014 Dresden, Germany Scientific -- International

8 Magnetic carrier Conference

(Poster) F. Ludwig (TUBS)

Resolving particle size modality in bi-modal

iron oxide nanoparticle suspensions

June 2014 Dresden, Germany Scientific -- International

9

Scientific & Clinical Applicatuons of Magnetic

Carriers Conference (Poster)

Q. A. Pankhurst (UCL), C.

Johansson (Acreo)

Estimating the power absorption of tailored

iron oxide nanoparticles from AC susceptibility

measurements

June 2014 Dresden, Germany Scientific -- International

10 UK Colloids Conference

(Invited)

Quentin Pankhurst

(UCL)

Translational R&D in Healthcare

Biomagnetics July 2014 London, UK Scientific -- International

11 Optimization and Inverse

Problems Workshop (Oral)

Uwe Steinhoff

(PTB)

Experimental Sensitivity Analysis of

Magnetorelaxometric Imaging

Sept 2014 Delft, Netherland Scientific -- International

12 FOM BioPhysics meeting

(Poster)

Leo J. van Ijzendoorn

(TUE)

On torque generation in superparamagnetic

particles (v1) Sept 2014 Veldhoven, Netherland Scientific -- National

13

1st meeting of the CNB nanobiomedicine iniciative

Workshop (Oral)

M. Puerto Morales (CSIC)

Nanometrology, Standardization Methods for the

synthesis of Magnetic Nanoparticles with

applications in biomedicine

October 2014 Madrid, Spain dissemination

towards industry -- International

14 48th DGBMT annual

conference (Poster)

K. Lüdtke-Buzug (UZL)

Characterization of Superparamagnetic

Nanoparticles using a Micro-CT Phantom: Estimation of Iron

October 2014 Hannover, Germany Scientific -- International

Page 53: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

53

Concentration in Ferrofluids

15 MoBi2014 Workshop¿?

(Oral)

Nicole Gehrke

(nanoPET) EU FP7: NanoMag October 2014 Jena, Germany

dissemination towards industry

-- International

16 Nanomedicine workshop

(Poster) Larss Nilsson

(SOLVE)

Helping nano-entities discover their nano-

identity October, 2014

Malmö University, Sweden

Scientific/not funded by NanoMag

-- International

17

18th Int. Conf. on Miniaturized Systems for

Chemistry and Life Sciences (MicroTAS 2014)

(Poster)

M. F. Hansen (DTU)

Lab-on-Blu-ray: Low-cost analyte

detection on a disk

Oct. 26 - Oct. 30, 2014

San Antonio, Texas, USA

Scientific -- International

18 Biosensor conference

(Poster) M. F. Hansen

(DTU)

Comparison of optomagnetic and AC

susceptibility readouts in a

magnetic nanoparticle

agglutination assay for detection of C-

reactive protein

May 25-27, 2016

Gothenburg Scientific -- International

19

Brokerage Event for Nanotechnologies,

Advanced Materials, Biotechnology and

Advanced Manufacturing and Processing

(Oral)

Lars Nilsson (SOLVE)

Nanomedicin therapy for cancer

November 2014 Brussels, Belgium

dissemination towards

industry/not funded by NanoMag

-- International

20

Brokerage Event for Nanotechnologies,

Advanced Materials, Biotechnology and

Lars Nilsson (SOLVE)

Next generation tools for risk governance of

nanomaterial November 2014 Brussels, Belgium

dissemination towards

industry/not funded by

-- International

Page 54: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

54

Advanced Manufacturing and Processing

(Oral)

NanoMag

21 FOM BioPhysics meeting

(Poster)

Leo J. van Ijzendoorn

(TUE)

On torque generation in superparamagnetic

particles (v2) Jan 2015 Veldhoven, Netherland Scientific -- National

22 ICMS Outreach symposium

(Poster)

Leo J. van Ijzendoorn

(TUE)

On torque generation in superparamagnetic

particles (v2) Jan 2015 Eindhoven,Netherland Scientific -- International

23 Multifun Final Workshop

(Oral)

M. Puerto Morales (CSIC)

Improving Magnetic Properties of Ultrasmall

Iron Oxide Nanoparticles by

Biocompatible Coatings

Feb 2015 Madrid, Spain Scientific -- International

24 Multifun Final Workshop

(Poster)

M. Puerto Morales (CSIC)

Synthesis Strategies of Single-Core Magnetic

Nanoparticles Feb 2015 Madrid, Spain Scientific -- International

25 EMIM meeting

(Oral, Poster and Flyers)

Nicole Gehrke

(nanoPET)

EU FP 7: NanoMag – Standardization of

Analysis Methods for Magnetic Nanoparticles

March 2015 Tübingen, Germany Scientific 595 International

26 IWMPI Workshop

(Poster)

Nicole Gehrke

(nanoPET)

EU FP 7: NanoMag – Standardization of

Analysis Methods for Magnetic Nanoparticles

March 2015 Istambul, Turkey Scientific/Industry -- International

27 IWMPI Workshop

(Poster)

K. Lüdtke-Buzug (UZL)

Evaluation of a Cotton-Mouton Relaxometer for the Characterization of

Superparamagnetic Iron Oxide Nanoparticles

March 2015 Istambul, Turkey Scientific/Industry -- International

28 BME research day meeting

(Poster)

Leo J. van Ijzendoorn

(TUE)

Magnetic analysis of superparamagnetic

particles April 2015 Eindhoven,Netherland Scientific -- International

29 6th International Congress – Quentin Biomedical applications April 2015 Graz, Austria Scientific -- International

Page 55: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

55

BioNanoMed (Invited)

Pankhurst (UCL)

of magnetic nanoparticles

30 5th Zing Bionanomaterials

Conference (Invited)

Quentin Pankhurst

(UCL)

Translational R&D in Healthcare

Biomagnetics April 2015 Carvoeiro, Portugal Scientific -- International

31

ICMM-CNIC Workshop on Chemistry and molecular

imaging (Oral)

M. Puerto Morales (CSIC)

Nanometrology Standarization Methods

for Magnetic Nanoparticles

May 2015 Madrid, Spain Scientific -- International

32

FRONTIERS IN BIOMAGNETIC PARTICLES

Conference (Oral)

M. Puerto Morales (CSIC)

Effect of the transformations of nanoparticles in

biological matrices on their magnetic

properties

June 2015 Asheville, USA Scientific -- International

33

FRONTIERS IN BIOMAGNETIC PARTICLES

Conference (Poster)

M. Puerto Morales (CSIC)

Effect of the transformations of nanoparticles in

biological matrices on their magnetic

properties

June 2015 Asheville, USA Scientific -- International

34 EuroNanoForum Conference

(Exhibition Stand) A. Fornara

(SP)

NanoMag presentation - top 10 EU projects in

the Future Flash! Best Project competition

June 2015 Riga, Latvia Scientific/Industry -- International

35 EuroNanoForum Conference

(Poster) Larss Nilsson

(SOLVE)

Helping nano-entities discover their nano-

identity June 2015 Riga, Latvia Scientific/Industry -- International

36 EuroNanoForum Conference

(Poster) Larss Nilsson

(SOLVE)

SOLVE the challenges of nanomaterial properties and performance

June 2015 Riga, Latvia Scientific/Industry -- International

37 FerroFluid Workshop 2015

(Poster) Uwe

Steinhoff Aspects of a standardized

June 2015 Rostock, Germany Scientific -- International

Page 56: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

56

(PTB) characterization and description of nanomagnetic

suspensions for biomedical applications

38 FerroFluid Workshop 2015

(Oral)

Uwe Steinhoff

(PTB)

Imaging characterization of

magnetic nanoparticles for Magnetic Particle Imaging using offset

field supported Magnetic Particle

Spectroscopy

June 2015 Rostock, Germany Scientific -- International

39 10th Materials Days

symposium (Invited)

M. Puerto Morales (CSIC)

Synthesis methods to prepare single- and multi-core iron oxide

nanoparticles for biomedical applications

June 2015 Rostock, Germany Scientific -- International

40 10th Materials Days

symposium (Invited)

Quentin Pankhurst

(UCL)

Nanomagnetism in Biology and Medicine

June 2015 Rostock, Germany Scientific -- International

41 10th Materials Days

symposium (Oral*)

Christer Johansson

(Acreo)

NanoMag project - standardization of

analysis methods for magnetic nanoparticles.

June 2015 Rostock, Germany Scientific -- International

42 ICM Conference

(Invited)

M. Puerto Morales (CSIC)

Efficient and safe magnetic iron oxide

nanoparticles for biomedicine

July 2015 Barcelona, Spain Scientific -- International

43 ICM Conference

(Oral) O. Kazakova

(NPL)

Scanning gate microscopy of a domain

wall nanosensor July 2015 Barcelona, Spain Scientific -- International

44 ICM Conference

(Oral) Christer

Johansson Static and dynamic

magnetization behavior July 2015 Barcelona, Spain Scientific -- International

Page 57: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

57

(Acreo) of magnetic multi-core nanoparticles

45 ICM Conference

(Oral)

Quentin Pankhurst

(UCL)

Field and frequency dependence of the SAR/ILP value in

magnetic hyperthermia using magnetic multi-

and single core particles

July 2015 Barcelona, Spain Scientific -- International

46 ICM Conference

(Oral) P. Svedlindh

(UU)

On-chip attomol level detection of proteins

using forced magnetic bead transport

July 2015 Barcelona, Spain Scientific -- International

47 ICM Conference

(Oral) M. F. Hansen

(DTU)

Optomagnetic read-out system for detection of pathogens based on magnetic nanobead

dynamic

July 2015 Barcelona, Spain Scientific -- International

48 ICM Conference

(Oral)

Christer Johansson

(Acreo)

Static and dynamic magnetization behavior of magnetic multi-core

nanoparticles

July 2015 Barcelona, Spain Scientific -- International

49 ICM Conference

(Poster) P. Svedlindh

(UU)

Highly anisotropic dynamical magnetic properties of needle-shaped arrays of iron

oxide nanocubes

July 2015 Barcelona, Spain Scientific -- International

50 ICM Conference

(Poster)

L.Fernández-Barquín

(UC)

SANS, Mössbauer and magnetic

characterization of interacting iron oxide

nanoparticles

July 2015 Barcelona, Spain Scientific -- International

51 ICM Conference

(Poster) Quentin

Pankhurst Field and frequency dependency on the

July 2015 Barcelona, Spain Scientific -- International

Page 58: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

58

(UCL) SAR value in magnetic hyperthermia using magnetic multi- and single-core particles

52 ICM Conference

(Poster)

M. Puerto Morales (CSIC)

Synthesis Strategies of Single-Core Magnetic

Nanoparticles July 2015 Barcelona, Spain Scientific -- International

53 ICMAT2015 Conference

(Invited)

M. Puerto Morales (CSIC)

Effect of the Counter-Ions and the Solvent in

the Synthesis of Magnetite Nanocrystals

by Oxidative Precipitation

July 2015 Singapore Scientific -- International

54 XXI IMEKO World Congress

(Oral)

Uwe Steinhoff

(PTB)

Classification of analysis methods for characterization of

magnetic nanoparticle properties

August 2015 Prague, Check

republic Scientific -- International

55

The International Conference on the Applications of the

Mössbauer Effect – ICAME (Invited)

Quentin Pankhurst

(UCL)

Biomedical applications of magnetic

nanoparticles Sept 2015 Hamburg, Germany Scientific -- International

56

The International Conference on the Applications of the

Mössbauer Effect – ICAME (Poster)

M. F. Hansen (DTU)

Biomedical applications of magnetic

nanoparticles Sept 2015 Hamburg, Germany Scientific -- International

57 Wyatt Europe

workshop/User meeting (Invited)

Larss Nilsson (SOLVE)

nanoparticles, macromolecules and

proteins Sept 2015 Dernbach, Germany Industry -- National

58 UK Regenerative Medicine

Platform - Safety Hub Workshop - Nanoparticles

Quentin Pankhurst

(UCL)

Biomedical applications of magnetic

nanoparticles Sept 2015 Liverpool, UK Scientific -- International

Page 59: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

59

for Cell Tracking (Invited)

59 29. Treffpunkt

Medizintechnik Conference (Oral)

Nicole Gehrke

(nanoPET)

EU FP 7: NanoMag – Standardization of

Analysis Methods for Magnetic Nanoparticles

Sept 2015 Berlin, Germany Scientific/Industry -- National

60 49th DGBMT annual

Conference (Poster)

K. Lüdtke-Buzug (UZL)

Synthesis of Superparamagnetic Iron

Oxide Nanoparticles under Ultrasound

Control

Sept 2015 Luebeck, Germany Scientific/Industry -- International

61 FOM BioPhysics meeting

(Poster)

Leo J. van Ijzendoorn

(TUE)

On torque generation in superparamagnetic

particles (v3) Sept 2015 Veldhoven, Netherland Scientific -- National

62 NanoCity meeting 2015

(poster)

Leo J. van Ijzendoorn

(TUE)

On torque generation in superparamagnetic

particles (v3) Sept 2015

Amersfoort, Netherland

Scientific/industry -- International

63 EMN Workshop 2015

(Invited)

Olga Kazakova

(NPL)

Novel Graphene-based Nanosensors

Sept 2015 San Sebastián, Spain Scientific -- International

64 ANMM Workshop

(Invited)

Olga Kazakova

(NPL)

Domain-wall based magnetic nanosensors

Sept 2015 Iasi, Romania Scientific -- International

65

ISO Technical Committee 229 "Nanotechnologies",

Working Group 4 "Material Specifications"

(Oral)

Uwe Steinhoff

(PTB)

Nanometrology – Standardization

Methods for Magnetic

Nanoparticles

Sept 2015 Edmonton Scientific -- International

66

BIOTECHNICA (industrial fair) oral

Joachim Teller, Fritz Westphal

Representing NanoMag project

October 2015 Hannover Scientific -- International

67 Nanocon (Invited)

M. Puerto Morales

Prospects for magnetic

Oct 2015 Brno Scientific -- International

Page 60: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

60

(CSIC) nanoparticles in in vivo biomedical

applications: synthesis,

biodistribution and degradation

68

RadioMag COST project meeting

(Oral)

Christer Johansson

(Acreo)

EU FP7 NanoMag project -

standardization of analysis methods for

magnetic nanoparticles.

Oct 2015 Limassol Scientific -- International

69

49th DGBMT annual conference

(Oral)

Uwe Steinhoff

(PTB)

Characterizing the imaging performance of magnetic tracers by Magnetic Particle Spectroscopy in an

offset field

Sept. 2015

Luebeck Scientific -- International

70 Contrast Media Research

(Oral)

F. Wiekhorst

(PTB)

Magnetic Nanoparticles in

Biomedicine - how magnetic

measurements support their application

November, 2015

Berlin Scientific -- International

71 IWMPI (Poster)

Uwe Steinhoff

(PTB)

Imaging Characterization of

MPI Tracers Employing Offset

Measurements in a two Dimensional Magnetic Particle

March 2016 Lübeck Scientific -- International

Page 61: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

61

Spectrometer

72 IWMPI (Poster)

F. Wiekhorst

(PTB)

Determining magnetic impurities

and nonspecific magnetic

nanoparticle adhesion of MPI

phantom materials

March 2016 Lübeck Scientific -- International

73 IWMPI (Poster)

Nicole Gehrke

(nanoPET)

Diffusion-Controlled Synthesis of

Magnetic Nanoparticles

March 2016 Lübeck Scientific -- International

74

16 TH INTERNATIONAL CONFERENCE ON SMALL-

ANGLE SCATTERING (Poster)

A.F. Thünemann

(BAM)

Metrology of magnetic iron oxide

nanoparticles

September 2015

Berlin Scientific -- International

75

Internat. Workshop on Magnetic Particle Imaging

(IWMPI 2016) (Poster)

F. Ludwig (TUBS)

Dependence of Brownian and Neel relaxation times on

magnetic field

March 2016

Lübeck Scientific -- International

76

15th German Ferrofluid Workshop

(Poster)

F. Ludwig (TUBS)

Magnetic-field dependence of

Brownian and Neel relaxation times on

ac magnetic field

June 2016 Rostock Scientific -- International

77

15th German Ferrofluid Workshop

(Poster)

L. Fernández-

Barquín (UC)

Mossbauer, SANS and magnetic

characterization of interacting iron oxide

nanoparticles

June 2016 Rostock Scientific -- International

78 Next-Generation

Nanomagnetic Medicine M. Puerto Morales

Preparation of magnetic

Nov 2015 Japan Scientific -- International

Page 62: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

62

Meeting,JAIST (Oral) (CSIC) nanocrystals for biomedical applications

79

Next-Generation Nanomagnetic Medicine

Meeting,JAIST (Oral)

M. Puerto Morales (CSIC)

The fate of magnetic nanoarticles in

biological systems: biodistribution and

transformations over time

Nov 2015 Japan Scientific -- International

80

Workshop: Magnetic Nanoparticles for

biomedical applications, ICMM (Oral)

M. Puerto Morales (CSIC)

The Nanomag Project Dec 2015 Madrid Scientific -- International

81

Workshop: Magnetic Nanoparticles for

biomedical applications, ICMM (Oral)

M. Puerto Morales (CSIC)

Synthesis of irregular shaped iron oxide

magnetic nanoparticles and

study of their magnetic properties.

Dec 2015 Madrid Scientific -- International

82

Proc. 19th Int. Conf. on Miniaturized Systems for

Chemistry and Life Sciences (MicroTAS 2015)

(Poster)

M. F. Hansen (DTU)

Integration of agglutination assay

for protein detection in microfluidic disc

using Blu-ray optical pickup unit and

optical fluid scanning

October, 2015 Geongju, Korea, Scientific -- International

83 Joint MMM-Intermag

(Oral)

Olga Kazakova

(NPL)

Detection of a magnetic bead by

hybrid nanodevices using scanning gate

microscopy

Jan 2016 San Diego, US Scientific -- International

Page 63: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

63

84 Joint MMM-Intermag

(Poster)

Olga Kazakova

(NPL)

Magnetic particle nanosensing by

nucleation of domain walls in ultra-thin

CoFeB/Pt

Jan 2016 San Diego, US Scientific -- International

85 IWMPI (Poster)

Nicole Gehrke

(nanoPET)

Diffusion-Controlled Synthesis of

Magnetic Nanoparticles

March 2016 Lübeck Scientific -- International

86

International Conference on Fine Particle

Magnetism (ICFPM) NIST, (Oral)

M. F. Hansen (DTU)

Characterization of fine particles using

optomagnetic measurements

June 13-17, 2016

Maryland, USA

Scientific -- International

87 ICMS Outreach

symposium, TUe (Poster)

Leo J. van Ijzendoorn

(TUE)

On torque generation in

superparamagnetic particles (v3)

Jan 2016 Eindhoven Scientific -- International

88

International Workshop on Magnetic Particle

Imaging (IWMPI) (Poster)

K. Lüdtke-Buzug (UZL)

MPS study on new MPI tracer material

March 2016

Lübeck Scientific -- International

89

2016 EU-Japan Collaborative Research

on Nanomagnetic Medicine workshop, UCL

(Oral) E91:E105

M. Puerto Morales (CSIC)

Effect of magnetic nanoparticle

clustering and dipolar interactions in

heating efficiency

9-10 May 2016 London, UK Scientific -- International

90

Reunion bienal del grupo especializado de qumica

inorgánica del estado sólido de la RSEQ

(Invited)

M. Puerto Morales (CSIC)

Perspectives in the use of magnetic nanoparticles in

cancer diagnosis and treatment

20-22 June 2016

Torremolinos, Malaga

Scientific -- International

Page 64: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

64

91

2nd International Conference on Polyol Mediated Synthesis, University of Shiga

Prefecture (Oral)

M. Puerto Morales (CSIC)

Polyol mediated synthesis to obtain

Single-Core and Flower-like shaped

Multi-Core magnetite nanoparticles

July 11-13, 2016

Hikone, Japan, Scientific -- International

92

International Conference on Hyperfine Interactions

and their Applications (HYPERFINE 2016) (Invited Plenary)

Quentin Pankhurst

(UCL)

Biomedical applications of

magnetic nanoparticles

July 2016 Leuven, Belgium Scientific -- International

93

8th Joint European Magnetic Symposia -

JEMS2016 (Poster)

L. Fernández-

Barquín (UC)

Influence of Coating thickness on the

magnetic properties of Iron-Oxide nanoparticles

21-26 August 2016

Glasgow, UK. Scientific -- International

94

11th International Conference on the

Scientific and Clinical Applications of Magnetic

Carriers 2016 (Poster)

Uwe Steinhoff

(PTB)

Interpreting static and dynamic

magnetization behavior of magnetic

nanoparticles in terms of magnetic

moment and energies

May, 2016 Vancouver Scientific -- International

95

11th International Conference on the

Scientific and Clinical Applications of Magnetic

Carriers 2016 (Poster)

F. Ludwig (TUBS)

Standardization of the analysis of single-

core magnetic nanoparticles

May, 2016 Vancouver Scientific -- International

96 11th International C. Grüttner Particle size- and May 31-June 4, Vancouver Scientific -- International

Page 65: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

65

Conference on the Scientific and Clinical

Applications of Magnetic Carriers (Poster)

(MM) concentration-dependent

separation of magnetic

nanoparticles

2016

97

11th International Conference on the

Scientific and Clinical Applications of Magnetic

Carriers 2016 (Poster)

L. Fernández-

Barquín (UC)

Numerical inversion methods to analyze magnetization data

May, 2016 Vancouver Scientific -- International

98

International Symposium on Field-and-Flow-Based

Separations (FFF2016) (Oral)

F. Wiekhorst

(PTB)

A Novel Magnetic FFF Detector for the

Quantification and Characterization of

Magnetic Nanoparticles

2016 Dresden Scientific -- International

99

International Conference on Fine Particle

Magnetism 2016 (Oral)

L. Fernández-

Barquín (UC)

Spin coupling in an iron oxide

nanoparticle ensemble analyzed

with polarized neutron scattering

2016 Gaithersburg Scientific -- International

100 EMSA 2016

(Oral)

Olga Kazakova

(NPL)

Domain Wall Nanosensors Based on Ultra-thin CoFeB

Films

2016 Torino Scientific -- International

101 EMSA 2016

(Invited)

Olga Kazakova

(NPL)

Domain-wall based magnetic

nanosensors for magnetic bead

2016 Torino Scientific -- International

Page 66: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

66

detection

102

European Magnetic Sensors and Actuators

(EMSA) conference, http://www.emsa2016.it/

(Oral)

M. F. Hansen (DTU)

Planar Hall effect bridges for magnetic

field sensing and biosensing

July 12-15, 2016

Torino Scientific -- International

103

22nd International Conference on DNA

Computing and Molecular Programming

(DNA22) (Poster)

M. F. Hansen (DTU)

Optomagnetic studies of pH-

switchable nanoparticles

agglutination via triplex DNA formation

4-8 September 2016

Munich, Germany Scientific -- International

104

The 20th International Conference on

Miniaturized Systems for Chemistry and Life

Sciences (Poster)

M. F. Hansen (DTU)

Optomagnetic studies of pH-

switchable nanoparticles

agglutination via triplex DNA

9-13 October 2016

Dublin, Ireland Scientific -- International

105 INTERMAG

(Oral)

M. Puerto Morales (CSIC)

Magnetite Nanoparticles

Assembled in Flower-like Structures with Tunable Magnetic Properties from

Superparamagnetic to Ferrimagnetic

24-28 April 2017

Dublin Scientific -- International

106 INTERMAG

(Invited)

M. Puerto Morales (CSIC)

Standardization methods for the

synthesis of single-core and multi-core

24-28 April 2017

Dublin Scientific -- International

Page 67: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

67

magnetic nanoparticles for

medical applications

107

Workshop on magnetic nanoparticles for

hyperthermia - experiments and

simulations (Oral)

M. Puerto Morales (CSIC)

Standardizing the synthesis of magnetic

nanoparticles

18-20 January 2017

Santiago de Compostela, Spain

Scientific -- International

108

Magnetic carrier Conference 2016

(Poster)

F. Ludwig (TUBS)

Size analysis of single-core magnetic

nanoparticles June 2016 Vancouver Scientific -- International

109

Magnetic carrier Conference 2016

(Oral)

F. Ludwig (TUBS)

Dual-frequency magnetic particle

imaging of the Brownian particle

contribution

June 2016 Vancouver Scientific -- International

110

Magnetic carrier Conference 2016

(Poster)

F. Ludwig (TUBS)

Effect of alignment of easy axes on dynamic

magnetization of immobilized

magnetic nanoparticles

June 2016 Vancouver Scientific -- International

111

Magnetic carrier Conference 2016

(Poster)

F. Ludwig (TUBS)

Harnessing viscosity effects to taylor the dynamic magnetic

response of magnetic nanoparticles

June 2016 Vancouver Scientific -- International

112 Intermag 2017

(Oral)

F. Ludwig (TUBS) Christer

Analysis of ac susceptibility spectra

for the April 2017 Dublin Scientific -- International

Page 68: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

68

Johansson (Acreo)

characterization of magnetic

nanoparticles

113 Intermag 2017

(Poster)

F. Ludwig (TUBS) Christer

Johansson (Acreo)

The anisotropy of the ac susceptibility of

immobilized magnetic

nanoparticles – the influence of intra-

potential-well contribution on the

ac susceptibility spectrum

April 2017 Dublin Scientific -- International

114

VIII Meeting of the Spanish Users Society

(SETN2016) (Oral)

L. Fernández-

Barquín (UC)

Spin coupling in magnetic

nanoparticle ensembles analyzed with polarized SANS

26th-29th June 2016

Bilbao, Spain Scientific -- International

115

14th International Conference on Magnetic

Fluids (Poster)

Uwe Steinhoff

(PTB)

Finding the magnetic size distribution of

magnetic nanoparticles from

magnetization measurements via

the iterative kaczmarz algorithm

July, 2016 Ekaterinburg Scientific -- International

116 BMT 2016

(Poster)

F. Wiekhorst

(PTB)

Magnetic Characterization of Phantom Materials

by Magnetic Particle Spectroscopy

2016 Basel Scientific -- International

Page 69: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

69

117 MMM 2016

(Oral)

Olga Kazakova

(NPL)

Magnetic scanning gate microscopy of CoFeB lateral spin

valve

2016 San Diego Scientific -- International

118 MMM 2016

(Oral)

Olga Kazakova

(NPL)

Local studies of domain wall

dynamics using anomalous Nernst

effect

2016 San Diego Scientific -- International

119 MMM 2016

(Oral)

Olga Kazakova

(NPL)

Ultrasensitive detection of single

iron oxide nanoparticles by

nucleation of domain walls in CoFeB nanostructures

2016 San Diego Scientific -- International

120

UK Institute of Physics, Medical Physics Group

Workshop on Dissemination and

Impact (Invited)

Quentin Pankhurst

(UCL)

Translational R&D in Nanoparticulate Medical Devices

21 Oct 2016 London, UK Scientific -- International

121 SF Nano Annual Meeting

(Invited)

Quentin Pankhurst

(UCL)

Magnetic Nanoparticles for

Sentinel Node Detection

12-14 Dec 2016

Paris, France Scientific -- International

122

SEPnet Student-led Conferences: Functional

scanning probe techniques

(Oral)

Olga Kazakova

(NPL)

V-shaped domain wall probes for

calibrated magnetic force microscopy

March, 2017 Southampton Scientific -- International

Page 70: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

70

123

SEPnet Student-led Conferences: Functional

scanning probe techniques

(Oral)

Olga Kazakova

(NPL)

Magntic Force microscopy imaging using a domain wall

March, 2017 Southampton Scientific -- International

124 Intermag 2017

(Invited)

Olga Kazakova

(NPL)

Current Induced Domain Wall Motion

in Cylindrical Nanowires

24th-28th April 2017

Dublin Scientific -- International

125 Intermag 2017

(Oral)

Olga Kazakova

(NPL)

Magnetic Force microscopy imaging using a domain wall

24th-28th April 2017

Dublin Scientific -- International

126 Intermag 2017

(Oral)

Olga Kazakova

(NPL)

Controllable multi-stable probes with low/high magnetic

moment

24th-28th April 2017

Dublin Scientific -- International

127 Intermag 2017

(Poster)

Olga Kazakova

(NPL)

Demonstration and metrology of a

magnetic nanoparticle sensor

using anomalous Nernst effect read-

out

24th-28th April 2017

Dublin Scientific -- International

128 TOPO 2017

(Poster)

Olga Kazakova

(NPL)

Calibrated Magnetic Force Microscopy with Domain Wall

Probes

April, 2017 San Francisco Scientific -- International

129

International Workshop on Magnetic Particle

Imaging (IWMPI) (Poster)

K. Lüdtke-Buzug (UZL)

Investigation on new MPI tracer material

March 2017 Praque Scientific -- International

Page 71: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

71

130

International Baltic Conference on

Magnetism (Invited)

Quentin Pankhurst

(UCL)

Biomedical Applications of

Magnetic Nanoparticles

21-23 August 2017

Svetlogorsk, Russia Scientific -- International

131 Euroanalysis 2017

(Oral) M. F. Hansen

(DTU)

Optomagnetic Sequence-Specific

Detection of Dengue Target DNA

Aug. 28 – Sep 1., 2017

Stockholm, Sweden Scientific -- International

132

Euroanalysis 2017, Aug. 28 – Sep 1., 2017,

(Oral)

M. F. Hansen (DTU)

An integrated lab-on-a-disc approach to

detect inflammatory biomarkers from

whole blood

Aug. 28 – Sep 1., 2017

Stockholm, Sweden Scientific -- International

133

7th Symposium on Nucleic Acid Chemistry

and Biology (Poster)

M. F. Hansen (DTU)

Dual kinetic and mechanistic profiling

of rolling circle amplification using

real-time optomagnetic studies

Sep. 3-6, 2017 Cambridge, UK Scientific -- International

134

43rd International Conference on Micro and

NanoEngineering (MNE2017)

(Oral)

M. F. Hansen (DTU)

Automated rolling circle amplification and optomagnetic

product detection in an injection molded all-polymer chip –

optimization of amplification temperature

Sep. 18-22, 2017

Braga, Portugal Scientific -- International

135

German Ferrofluid Workshop in Dresden

(Oral)

F. Ludwig (TUBS)

The anisotropy of the ac susceptibility of

magnetic July 2017 Dresden Scientific -- International

Page 72: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

72

nanoparticle suspensions

136 MMM 2017

(Oral)

F. Wiekhorst

(PTB)

Towards Quantitative Magnetic Particle

Imaging: A Comparison with Magnetic Particle

Spectroscopy

6-10 Nov, 2017 Pittsburgh, USA Scientific -- International

137 COST-RADIOMAG2017

(Oral)

Uwe Steinhoff

(PTB)

Steel balls as heating phantoms in

magnetic hyperthermia

27-28 April 2017

Bilbao Scientific -- International

138 IBCM 2017

(Invited)

M. Puerto Morales (CSIC)

Standardization methods for the

synthesis of magnetic nanoparticles for

medical applications

20-24 August, 2017

Kaliningrad Scientific -- International

139 ICMAT17 de Singapur

(Oral)

M. Puerto Morales (CSIC)

Preparation of bimetallic magnetic

nanocrystals by oxidative

precipitation

18-23 June, 2017

Singapore Scientific -- International

S1 seminar Gladis

Amalia Ruiz Estrada

Toxicity and biodistribution of

PEG coated magnetic nanoparticles after injection in Wistar

rats

11/04/2014 Facultad de

Ciencias, University of Santander

Scientific 30 people National

S2 Seminar M.P.

Morales Nanotechnology for the detection and

23/03/2015 Universidad Carlos

III de Madrid Scientific 50 people National

Page 73: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

73

treatment of cancer

S3 seminar Diego Alba

Venero

Study of the super spin glass-

superferromagnetism transtion with

neutrons

27/02/2015 Facultad de

Ciencias, University of Cantabria

Scientific 15 people National

S4 seminar Philipp Bender

Magnetic particle nanorheology: Novel approaches based on

magnetization, optical transmission

and SANS measurements.

13/03/2015 Facultad de

Ciencias, University of Cantabria

Scientific 15 people National

S5 Seminar at Vinca institute Maria del

Puerto Morales

Magnetic nanoparticles for the

detection and treatment of cancer

25/09/2015 Belgrade, Serbia Scientific 20 people National

S6 Seminar Lucia

Gutierrez

Nanopartículas magnéticas para

aplicaciones biomédicas

15/05/2015

Colegio Escuela Profesional María

Auxiliadora, Zaragoza.

Scientific 50 National

S7 IBME, University of

Oxford Quentin

Pankhurst

Translational R&D in Healthcare

Biomagnetics 20/01/2015 Oxford, UK Scientific 60 National

S8 PTB L. Trahms,

U. Steinhoff NanoMag online PTB news Scientific --- National

S9

e-Learning, Module 2: Biomedical Applications

of Magnetic Nanoparticles

Oliver Posth, Uwe Steinhoff, Michael Lingard,

NanoMag online NPL e-learning

courses Scientific --- National

Page 74: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

74

Olga Kazakova

S10 Seminar at Inst. Laue-

Langevin Philipp Bender

Polarized SANS as advanced

characterization technique within the

NanoMag project

07/04/2016 Grenoble, France Scientific --- National

S11 Seminar Lucia

Gutierrez

Nanotoxicity: Is our body able to deal

with magnetic particles?

21/10/2015 Young Scientist

MeetingsICMM/CSIC Scientific 30 National

S12 Seminar Lucia

Gutierrez

Detection of magnetic

nanoparticles for biomedical

applications in biological matrices

11/02/2015 Facultad de

Ciencias, University of Zaragoza

Scientific 15 people National

S13 The Embassy of Japan in

the UK Quentin

Pankhurst

Biomedical applications of

magnetic nanoparticles’,

presented at ‘Japan-UK Joint Workshop on Life Science and

Biomedical Engineering’,

03/12/2015 London, UK Scientific --- National

S14 University of York Quentin

Pankhurst

Translational R&D in Nanoparticulate

Medical Devices’, presented at

'Nanostructures for

04/12/2015 York, UK Scientific --- National

Page 75: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

75

Medical Applications - Opportunities,

Challenges and New Approaches’,

S15 University of Florida Quentin

Pankhurst

‘Healthcare Biomagnetics’,

presented to the Institute for Cell Engineering & Regenerative

Medicine, University of Florida, Gainesville

FL, USA, 16th February 2016.

16/02/2016 Florida, USA Scientific --- National

S16 UCL Quentin

Pankhurst

An Academic’s Perspective on

Translational R&D’, presented to the

OSNIRO Workshop on Venture Capital

Funding,

01/03/2016 London, UK Scientific --- National

S17 Summer School UAM,

Magnetic nanoparticles, M.P.

Morales Magnetic colloids 42539 Madrid Scientific 25 National

S18

Summer school, Zaragoza University, Nanoscience:

New challenges and opportunities for

biotechnology

Sabino Veintemillas

Synthesis routes for the preparation of uniform magnetic

nanoparticles

19-21/07/16 Jaca, Huesca, Spain Scientific 50 National

S19 CSIC Olga

Kazakova

Domain-wall based magnetic

nanosensors for 19/10/2016 Madrid, Spain Scientific 30 National

Page 76: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

76

metrology and bio applications

S20

The IEEE Magnetic society 2017 Summer

School

Puerto Morales

Magnetics for bio applications

June 19 - 23 2017

Universidad International

Menendez Pelayo (UIMP), Santander,

Spain.

Scientific 100 National

S21

Summer school “Materials for Biomedical

Applications”- MATBIO2017

Puerto Morales

Magnetic nanoparticles for

therapeutic Applications

19-22 June 2017

Materials Science Institute of

Barcelona (ICMAB-CSIC)

Scientific 100 National

S22 KAUST Olga

Kazakova

Domain-wall based magnetic

nanosensors for metrology and bio

applications

November, 2016

Jeiddah, Saudi Arabia

Scientific 200 National

S23 PTB, Germany Hector

Corte-Leon

Magnetic domain wall-based

nanosensors 2017

Braunschweig, Germany

Scientific 50 National

S24 Leeds Univ Hector

Corte-Leon

Magnetic domain wall-based

nanosensors 2017 Leeds, UK Scientific 30 National

S25 seminar Olga

Kazakova

Domain-wall based magnetic

nanosensors for metrology and Life

Science applications

30-may-17 Institut Neel (CNRS)

Grenoble, France Scientific 50 National

S26 Departmental seminar Quentin

Pankhurst

Biomedical Applications of

Magnetic Nanoparticles

22-mar-17 University of Leeds Scientific 45 National

Page 77: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

77

S27 Seminar Uwe

Steinhoff

Standardization of properties and

characterization of magnetic

nanoparticles: status and perspectives

9 December 2016

AGH, Academic Center of Materials

and Nanotechnology, Kraków, Poland

Scientific 30 National

S28

IEC SC62D/JWG22 and ISO TC121/SC3/JWG14

meeting

Uwe Steinhoff

Metrology and standardization of

magnetic nanoparticles

9 February 2017

PTB, Berlin Scientific 25 National

S29 MagNaStand Industrial Stakeholder Workshop

Uwe Steinhoff

MagNaStand – Towards an ISO

standard for magnetic

nanoparticles

4 July 2017 PTB, Berlin Scientific 25 National

S30 MagNaStand Industrial Stakeholder Workshop

Uwe Steinhoff

Current ISO/TC229 WG4 activities

related to standardisation of

magnetic nanoparticles and

beads

4 July 2017 PTB, Berlin Scientific 25 National

S31 MagNaStand Industrial Stakeholder Workshop

James Wells

Standardisation of magnetic

nanoparticles – state of the art and future

needs

4 July 2017 PTB, Berlin Scientific 25 National

S32 MagNaStand Industrial Stakeholder Workshop

Quentin Pankhurst

Biomedical applications of

magnetic nanoparticles

4 July 2017 PTB, Berlin Scientific 25 National

Page 78: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

78

S33 MagNaStand Industrial Stakeholder Workshop

Craig Barton

Stakeholder needs in magnetic

nanoparticle related industry and research

– lessons learned from the NanoMag

project

4 July 2017 PTB, Berlin Scientific 25 National

Page 79: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

79

Section B (Confidential6 or public: confidential information to be marked clearly)

Part B1

This section is not applicable in the NanoMag project.

TEMPLATE B1: LIST OF APPLICATIONS FOR PATENTS, TRADEMARKS, REGISTERED DESIGNS, ETC.

Type of IP Rights7:

Confidential

Click on YES/NO

Foreseen embargo

date

dd/mm/yyyy Application

reference(s) (e.g.

EP123456)

Subject or title of application Applicant (s) (as on the application)

6 Note to be confused with the "EU CONFIDENTIAL" classification for some security research projects.

7 A drop down list allows choosing the type of IP rights: Patents, Trademarks, Registered designs, Utility models, Others.

Page 80: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

80

Part B2

Type of

Exploitable

Foreground

Description

of exploitable

foreground

Confi

dentia

l

Click

on

YES/

NO

Foreseen

embargo

date dd/mm/yy

yy

Exploitable

product(s) or

measure(s)

Sector(s) of

application

Timetable,

commercial or

any other use

Patents or other

IPR

exploitation

(licences) Owner & Other

Beneficiary(s) involved

1. Commercial exploitation of R&D results

magnetic nanoflower-shaped iron-oxide nanoparticles with citrate coating

YES 16.11.2016

IMAGING AND

HEAT-ASSISTED

THERAPY,

BIOSENSOR

M72.1.1,

C20.5.9

IMMEDIATELY NONE MICROMOD, CSIC

2. Commercial exploitation of R&D results

HIGH FREQUENCY

AC

SUSCEPTOMETER

YES M72.1.1,

M72.1.9,

C20.5.9

2018 FILED IN 2010

(E.G.

SE1050526

A1)

RISE ACREO

1. Summary: “Magnetic Nanoflower-Shaped Iron-Oxide Nanoparticles with Citrate coating”

micromod (MM) has established a standard-operating procedure (SOP) for the synthesis of magnetic nanoflower-shaped iron oxide nanoparticles

based on a previous literature report (Lartigue et al. 2012, doi: 10.1021/nn304477s) by a thermal decomposition process in a polyol reaction medium.

Excellent reproducibility in size and yield along with consistent magnetic properties was achieved. CSIC has the developed a citrate coating for

magnetic nanoparticles, which was used by MM to stabilize the magnetic nanoflower-shaped iron-oxide nanoparticles and to enhance their

biocompatibility for utilization in life-sciences and analytics. Moreover, an application in medical imaging and heat-assisted therapies or a

combination of both is of particular importance. The synthesis amended by an additional coating based on micromod’s background has been

published in partial (Gavilán et al. Part. Part. Syst. Charact. 2017, 1700094).

Page 81: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

81

The citrate-coated particles will be available on webpage www.micromod.de by 01.01.2018 and have already been advertised on trade fairs like

Biotechnica as well as in key account communications with micromod customers. For the next three years micromod expects an annual revenue of 10

TEuro per acquired key customer.

2. Summary: “High Frequency AC susceptometer”

RISE Acreo has during the NanoMag project further developed a high frequency AC susceptometer to be used for dynamic magnetic measurements

of for instance dispersed MNP systems (but also for powder material or other solid samples). The start of the design and construction of this

instrument was during the EU FP7 NMP Nano3T project (focused on magnetic hyperthermia, 2008-2011). The instrument will be a valuable asset to

magnetic hyperthermia studies.

We have also added Key Exploitable Results (KER) information in the exploitation plan (deliverable D7.5) regarding a new sensing system (opto-

magnetic system) developed and verified at DTU in the project.

Page 82: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

82

4.3 Report on societal implications

A General Information (completed automatically when Grant Agreement number is entered.

Grant Agreement Number: 604448

Title of Project:

Nanometrology Standardization Methods for Magnetic (Nanoparticles

Name and Title of Coordinator:

Christer Johansson, Professor

B Ethics

1. Did your project undergo an Ethics Review (and/or Screening)?

• If Yes: have you described the progress of compliance with the relevant Ethics Review/Screening

Requirements in the frame of the periodic/final project reports?

Special Reminder: the progress of compliance with the Ethics Review/Screening Requirements should be

described in the Period/Final Project Reports under the Section 3.2.2 'Work Progress and Achievements'

No

0Yes 0No

2. Please indicate whether your project involved any of the following issues (tick box): YES RESEARCH ON HUMANS

• Did the project involve children? No

• Did the project involve patients? No

• Did the project involve persons not able to give consent? No

• Did the project involve adult healthy volunteers? No

• Did the project involve Human genetic material? No

• Did the project involve Human biological samples? No

• Did the project involve Human data collection? No

RESEARCH ON HUMAN EMBRYO/FOETUS

• Did the project involve Human Embryos? No

• Did the project involve Human Foetal Tissue / Cells? No

• Did the project involve Human Embryonic Stem Cells (hESCs)? No

• Did the project on human Embryonic Stem Cells involve cells in culture? No

• Did the project on human Embryonic Stem Cells involve the derivation of cells from Embryos? No

PRIVACY

• Did the project involve processing of genetic information or personal data (eg. health, sexual lifestyle,

ethnicity, political opinion, religious or philosophical conviction)?

No

• Did the project involve tracking the location or observation of people? No

RESEARCH ON ANIMALS

• Did the project involve research on animals? No

• Were those animals transgenic small laboratory animals? No

• Were those animals transgenic farm animals? No

• Were those animals cloned farm animals? No

• Were those animals non-human primates? No

RESEARCH INVOLVING DEVELOPING COUNTRIES

• Did the project involve the use of local resources (genetic, animal, plant etc)? No

• Was the project of benefit to local community (capacity building, access to healthcare, education etc)? No

DUAL USE

• Research having direct military use No

• Research having the potential for terrorist abuse No

Page 83: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

83

C Workforce Statistics

3. Workforce statistics for the project: Please indicate in the table below the number of people

who worked on the project (on a headcount basis).

Type of Position Number of Women Number of Men

Scientific Coordinator 1

Work package leaders 2 4

Experienced researchers (i.e. PhD holders) 22 39

PhD Students 3 15

Other

4. How many additional researchers (in companies and universities) were recruited

specifically for this project?

8

Of which, indicate the number of men:

3

Page 84: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

84

D Gender Aspects

5. Did you carry out specific Gender Equality Actions under the project?

Yes

No

6. Which of the following actions did you carry out and how effective were they?

Not at all

effective

Very

effective

Design and implement an equal opportunity policy Set targets to achieve a gender balance in the workforce Organise conferences and workshops on gender Actions to improve work-life balance Other:

7. Was there a gender dimension associated with the research content – i.e. wherever people were the

focus of the research as, for example, consumers, users, patients or in trials, was the issue of gender considered and

addressed?

Yes- please specify

No

E Synergies with Science Education

8. Did your project involve working with students and/or school pupils (e.g. open days,

participation in science festivals and events, prizes/competitions or joint projects)?

Yes- please specify

No

9. Did the project generate any science education material (e.g. kits, websites, explanatory booklets,

DVDs)?

Yes- please specify

No

F Interdisciplinarity

10. Which disciplines (see list below) are involved in your project?

Main discipline8:

Associated discipline8: Associated discipline8:

G Engaging with Civil society and policy makers

11a Did your project engage with societal actors beyond the research

community? (if 'No', go to Question 14)

Yes

No

11b If yes, did you engage with citizens (citizens' panels / juries) or organised civil society (NGOs,

patients' groups etc.)?

No

Yes- in determining what research should be performed

Yes - in implementing the research

Yes, in communicating /disseminating / using the results of the project

8 1.2, 1.3, 1.5, 2.2, 2.3, 3.1, 3.3.

Four electronic-learning modules developed in the project

focused on magnetic nanoparticles, standardization and

their applications

Open days at CSIC for pupils and public showing the concept of

magnetic nanoparticles

Page 85: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

85

11c In doing so, did your project involve actors whose role is mainly to organise the

dialogue with citizens and organised civil society (e.g. professional mediator;

communication company, science museums)?

Yes

No

12. Did you engage with government / public bodies or policy makers (including international

organisations)

No

Yes- in framing the research agenda

Yes - in implementing the research agenda

Yes, in communicating /disseminating / using the results of the project

13a Will the project generate outputs (expertise or scientific advice) which could be used by policy

makers?

Yes – as a primary objective (please indicate areas below- multiple answers possible)

Yes – as a secondary objective (please indicate areas below - multiple answer possible)

No

13b If Yes, in which fields? Enviroment, Food Safety, Public Health, Research and Innovation

Agriculture

Audiovisual and Media

Budget Competition

Consumers

Culture Customs

Development Economic and Monetary

Affairs Education, Training, Youth

Employment and Social Affairs

Energy

Enlargement

Enterprise Environment

External Relations

External Trade Fisheries and Maritime Affairs

Food Safety

Foreign and Security Policy Fraud

Humanitarian aid

Human rights

Information Society

Institutional affairs Internal Market

Justice, freedom and security

Public Health Regional Policy

Research and Innovation

Space Taxation

Transport

Page 86: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

86

13c If Yes, at which level?

Local / regional levels

National level

European level

International level

H Use and dissemination

14. How many Articles were published/accepted for publication in peer-

reviewed journals?

82

To how many of these is open access9 provided? 10

How many of these are published in open access journals? 10

How many of these are published in open repositories?

To how many of these is open access not provided? 72

Please check all applicable reasons for not providing open access:

publisher's licensing agreement would not permit publishing in a repository

no suitable repository available

no suitable open access journal available

no funds available to publish in an open access journal

lack of time and resources

lack of information on open access

other10: ……………

15. How many new patent applications (‘priority filings’) have been made? ("Technologically unique": multiple applications for the same invention in different jurisdictions

should be counted as just one application of grant).

0

16. Indicate how many of the following Intellectual

Property Rights were applied for (give number in each

box).

Trademark 0

Registered design 0

Other 0

17. How many spin-off companies were created / are planned as a direct result of

the project?

0

Indicate the approximate number of additional jobs in these companies:

18. Please indicate whether your project has a potential impact on employment, in comparison with

the situation before your project: Increase in employment, or In small & medium-sized enterprises

Safeguard employment, or In large companies

Decrease in employment, None of the above / not relevant to the project

Difficult to estimate / not possible to quantify

19. For your project partnership please estimate the employment effect resulting

directly from your participation in Full Time Equivalent (FTE = one person

working fulltime for a year) jobs:

Indicate figure:

9 Open Access is defined as free of charge access for anyone via Internet. 10 For instance: classification for security project.

Page 87: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

87

Difficult to estimate / not possible to quantify

I Media and Communication to the general public

20. As part of the project, were any of the beneficiaries professionals in communication or media

relations?

Yes No

21. As part of the project, have any beneficiaries received professional media / communication

training / advice to improve communication with the general public?

Yes No

22 Which of the following have been used to communicate information about your project to the

general public, or have resulted from your project?

Press Release Coverage in specialist press

Media briefing Coverage in general (non-specialist) press

TV coverage / report Coverage in national press

Radio coverage / report Coverage in international press

Brochures /posters / flyers Website for the general public / internet

DVD /Film /Multimedia Event targeting general public (festival, conference,

exhibition, science café)

23 In which languages are the information products for the general public produced?

Language of the coordinator English

Other language(s)

Question F-10: Classification of Scientific Disciplines according to the Frascati Manual 2002 (Proposed Standard

Practice for Surveys on Research and Experimental Development, OECD 2002):

FIELDS OF SCIENCE AND TECHNOLOGY

1. NATURAL SCIENCES

1.1 Mathematics and computer sciences [mathematics and other allied fields: computer sciences and other allied

subjects (software development only; hardware development should be classified in the engineering fields)]

1.2 Physical sciences (astronomy and space sciences, physics and other allied subjects)

1.3 Chemical sciences (chemistry, other allied subjects)

1.4 Earth and related environmental sciences (geology, geophysics, mineralogy, physical geography and other

geosciences, meteorology and other atmospheric sciences including climatic research, oceanography,

vulcanology, palaeoecology, other allied sciences)

1.5 Biological sciences (biology, botany, bacteriology, microbiology, zoology, entomology, genetics,

biochemistry, biophysics, other allied sciences, excluding clinical and veterinary sciences)

2 ENGINEERING AND TECHNOLOGY

2.1 Civil engineering (architecture engineering, building science and engineering, construction engineering,

municipal and structural engineering and other allied subjects)

2.2 Electrical engineering, electronics [electrical engineering, electronics, communication engineering and

systems, computer engineering (hardware only) and other allied subjects]

2.3. Other engineering sciences (such as chemical, aeronautical and space, mechanical, metallurgical and

materials engineering, and their specialised subdivisions; forest products; applied sciences such as geodesy,

industrial chemistry, etc.; the science and technology of food production; specialised technologies of

Page 88: PROJECT FINAL REPORT - CORDIS · modelling of MNP magnetic properties, especially the dynamic magnetic behaviour (for instance to be used in the magnetic hyperthermia field). Round

88

interdisciplinary fields, e.g. systems analysis, metallurgy, mining, textile technology and other applied

subjects)

3. MEDICAL SCIENCES

3.1 Basic medicine (anatomy, cytology, physiology, genetics, pharmacy, pharmacology, toxicology,

immunology and immunohaematology, clinical chemistry, clinical microbiology, pathology)

3.2 Clinical medicine (anaesthesiology, paediatrics, obstetrics and gynaecology, internal medicine, surgery,

dentistry, neurology, psychiatry, radiology, therapeutics, otorhinolaryngology, ophthalmology)

3.3 Health sciences (public health services, social medicine, hygiene, nursing, epidemiology)

4. AGRICULTURAL SCIENCES

4.1 Agriculture, forestry, fisheries and allied sciences (agronomy, animal husbandry, fisheries, forestry,

horticulture, other allied subjects)

4.2 Veterinary medicine

5. SOCIAL SCIENCES

5.1 Psychology

5.2 Economics

5.3 Educational sciences (education and training and other allied subjects)

5.4 Other social sciences [anthropology (social and cultural) and ethnology, demography, geography (human,

economic and social), town and country planning, management, law, linguistics, political sciences,

sociology, organisation and methods, miscellaneous social sciences and interdisciplinary , methodological

and historical S1T activities relating to subjects in this group. Physical anthropology, physical geography and

psychophysiology should normally be classified with the natural sciences].

6. HUMANITIES

6.1 History (history, prehistory and history, together with auxiliary historical disciplines such as archaeology,

numismatics, palaeography, genealogy, etc.)

6.2 Languages and literature (ancient and modern)

6.3 Other humanities [philosophy (including the history of science and technology) arts, history of art, art

criticism, painting, sculpture, musicology, dramatic art excluding artistic "research" of any kind, religion,

theology, other fields and subjects pertaining to the humanities, methodological, historical and other S1T

activities relating to the subjects in this group]